Publications by authors named "Changrong Wang"

40 Publications

The importance of perioperative and complication management in the treatment of pheochromocytoma crisis with venoarterial extracorporeal membrane oxygenation (V-A ECMO): a case report and review of the literature.

Perfusion 2021 Oct 7:2676591211049314. Epub 2021 Oct 7.

Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Purpose: In this article, we aimed to elaborate on perioperative and complication management in treatment of pheochromocytoma crisis with extracorporeal membrane oxygenation (ECMO).

Material And Methods: We report a case of relatively rare grant paraganglioma-induced pheochromocytoma crisis leading to severe circulatory failure, treated with venoarterial extracorporeal membrane oxygenation (V-A ECMO) as a bridge to curative adrenalectomy. Weaning of ECMO was followed by successful surgical removal of the tumor, and patient survival. However, distal ischemia of the cannulated leg occurred during ECMO operation, which eventually led to amputation. In addition, the patient developed new cerebral infarction and left hemiplegia, half a month after paraganglioma resection.

Conclusions: We believe that patients with pheochromocytoma crisis, who cannot maintain blood circulation, are eligible for V-A ECMO treatment. Moreover, care should be taken to prevent thrombosis and individualized and precise blood pressure management targets. Early detection and treatment of thrombosis is imperative to long-term prognosis of patients with ECMO.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/02676591211049314DOI Listing
October 2021

Step-by-step dual stimuli-responsive nanoparticles for efficient bacterial biofilm eradication.

Biomater Sci 2021 Oct 12;9(20):6889-6902. Epub 2021 Oct 12.

School of Pharmacy, Shandong New Drug Loading & Release Technology and Preparation Engineering Laboratory, Binzhou Medical University, 346 Guanhai Road, Yantai, 264003, P. R. China.

Biofilm-related bacterial infections are extremely resistant to antibiotics, mainly due to the impermeability of the intensive matrices, which allow the bacteria to survive antibiotic treatment. Herein, step-by-step dual stimuli-responsive azithromycin-loaded nanoparticles (CM/[email protected]) was constructed for efficient biofilm eradication. CM/[email protected] was prepared by the self-assembly of poly(ε-caprolactone)-polyethylene glycol-polyethylenimine (PCL-PEG-PEI) into cationic micelles and simultaneously encapsulated AZM into the hydrophobic core, which is further bound with -aconityl-D-tyrosine (CA-Tyr) through electrostatic interaction. Upon initial penetration, CM/[email protected] could show step-by-step dual-response to the microenvironment of biofilms. Firstly, the CA-Tyr shell rapidly responded to the acidic microenvironment and released D-Tyr to disassemble the biofilm mass. Then, the exposed cationic CM/AZM micelles could bind firmly to the negatively-charged bacteria cell membrane. With the enzymolysis of the PCL core, the rapidly releasing AZM could kill the bacteria over the depth of biofilms. Massive accumulation was observed in the infected lungs of biofilms-associated lung infection mice after the i.v. injection of CM/[email protected] under the 3D mode of the Imaging System. Reduced bacterial burden and alleviated fibrosis in the infected lungs were also obtained after treatment with CM/[email protected] mainly due to its intensive penetration in the biofilm and the orderly release of the biofilm dispersant and antimicrobial agents. In summary, this research developed an effective strategy for the treatment of blood-accessible biofilm-induced infections.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d1bm01038gDOI Listing
October 2021

Inhibition effects of long-term calcium-magnesia phosphate fertilizer application on Cd uptake in rice: Regulation of the iron-nitrogen coupling cycle driven by the soil microbial community.

J Hazard Mater 2021 08 19;416:125916. Epub 2021 Apr 19.

Key Laboratory of Original Agro-Environmental Pollution Prevention and Control, Agro-Environmental Protection Institute, Ministry of Agriculture and Rural Affairs, Tianjin 300191, People's Republic of China. Electronic address:

Cadmium (Cd) pollution in paddy soil seriously endangers food safety production. To investigate the effects and microbiological mechanisms of calcium-magnesium-phosphate (CMP) fertilizer application on Cd reduction in rice, field experiments were conducted in Cd-contaminated paddy soil. Compared with conventional compound fertilizer, CMP fertilizer treatments inhibited Cd uptake through plant roots, significantly decreasing Cd content in rice grains from 0.340 to 0.062 mg/kg. Soil pH and total Ca, Mg and P contents increased after CMP fertilizer application, resulting in a further decrease in soil available Cd content from 0.246 to 0.181 mg/kg. Specific extraction analysis recorded a decrease in both available Fe content and the ratio of nitrate to ammonium nitrogen, indicating that the soil Fe-N cycle was affected by the addition of CMP fertilizer. This finding was also recorded using soil bacterial community sequencing, with CMP fertilizer promoting the progress of nitrate-dependent Fe-oxidation driven by Thiobacillus (1.60-2.83%) and subsequent dissimilatory nitrate reduction to ammonium (DNRA) driven by Ignavibacteriae (1.01-1.92%); Fe-reduction driven by Anaeromyxobacter (3.09-2.23%) was also inhibited. Our results indicate that CMP fertilizer application regulates the Fe-N coupling cycle driven by the soil microbial community to benefit remediation of Cd contaminated paddy soil.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jhazmat.2021.125916DOI Listing
August 2021

Elaboration on the architecture of pH-sensitive surface charge-adaptive micelles with enhanced penetration and bactericidal activity in biofilms.

J Nanobiotechnology 2021 Aug 6;19(1):232. Epub 2021 Aug 6.

School of Pharmacy, Shandong New Drug Loading and Release Technology and Preparation Engineering Laboratory, Binzhou Medical University, 346 Guanhai Road, Yantai, 264003, People's Republic of China.

Background: Biofilm formation is one of the main reasons for persistent bacterial infections. Recently, pH-sensitive copolymers have fascinated incredible attention to tackle biofilm-related infections. However, the proper incorporation of pH-sensitive segments in the polymer chains, which could significantly affect the biofilms targeting ability, has not been particularly investigated. Herein, we synthesized three types of pH-sensitive copolymers based on poly (β-amino ester) (PAE), poly (lactic-co-glycolic acid) (PLA) and polyethylene glycol (PEG), PAE-PLA-mPEG (A-L-E), PLA-PAE-mPEG (L-A-E) and PLA-PEG-PAE (L-E-A) to address this issue.

Results: The three copolymers could self-assemble into micelles (M, M and M) in aqueous medium. Compared with M and M, placing the PAE at the distal PEG end of PLA-PEG to yield PLA-PEG-PAE (M) was characterized with proper triggering pH, fully biofilm penetration, and high cell membrane binding affinity. Further loaded with Triclosan (TCS), M/TCS could efficiently kill the bacteria either in planktonic or biofilm mode. We reasoned that PAE segments would be preferentially placed near the surface and distant from the hydrophobic PLA segments. This would increase the magnitude of surface charge-switching capability, as the cationic PAE would easily disassociate from the inner core without conquering the additional hydrophobic force arising from covalent linkage with PLA segments, and rapidly rise to the outermost layer of the micellar surface due to the relative hydrophilicity. This was significant in that it could enable the micelles immediately change its surface charge where localized acidity occurred, and efficiently bind themselves to the bacterial surface where they became hydrolyzed by bacterial lipases to stimulate release of encapsulated TCS even a relatively short residence time to prevent rapid wash-out. In vivo therapeutic performance of M/TCS was evaluated on a classical biofilm infection model, implant-related biofilm infection. The result suggested that M/TCS was effective for the treatment of implant-related biofilm infection, which was proved by the efficient clearance of biofilm-contaminated catheters and the recovery of surrounding infected tissues.

Conclusions: In summary, elaboration on the architecture of pH-sensitive copolymers was the first step to target biofilm. The M structure may represent an interesting future direction in the treatment of biofilm-relevant infections associated with acidity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12951-021-00980-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8344171PMC
August 2021

Foliar application of the sulfhydryl compound 2,3-dimercaptosuccinic acid inhibits cadmium, lead, and arsenic accumulation in rice grains by promoting heavy metal immobilization in flag leaves.

Environ Pollut 2021 Sep 17;285:117355. Epub 2021 May 17.

Agro-Environmental Protection Institute, Ministry of Agriculture and Rural Affairs, Tianjin, 300191, People's Republic of China. Electronic address:

Mixed pollution due to heavy metals (HMs), especially cadmium (Cd), lead (Pb), and arsenic (As), seriously endangers the safety of food produced in paddy soil. In the field experiments, foliar application of 2,3-dimercaptosuccinic acid (DMSA) at the flowering stage was found to significantly reduce the levels of Cd, Pb, total As, and inorganic As (iAs) in rice grains by 47.95%, 61.76%, 36.37%, and 51.24%, respectively, without affecting the concentration of metallonutrients, including Mn, K, Mg, Ca, Fe, and Zn. DMSA treatment significantly reduced the concentrations of Cd, Pb, and As in the panicle node, panicle neck, and rachis, while those in the flag leaves were significantly increased by up to 20.87%, 49.40%, and 32.67%, respectively. DMSA application promoted the transport of HM from roots and lower stalks to flag leaves with a maximum increase of 34.55%, 52.65%, and 46.94%, respectively, whereas inhibited the transport of HM from flag leaves to panicle, rachis, and grains. Therefore, foliar application of DMSA reduced Cd, Pb, and As accumulation in rice grains by immobilizing HMs in flag leaves. Thus, this strategy could act as a promising agronomic measure for the remediation of mixed HM contamination in paddy fields.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.envpol.2021.117355DOI Listing
September 2021

Correction: Co-delivery of anionic epitope/CpG vaccine and IDO inhibitor by self-assembled cationic liposomes for combination melanoma immunotherapy.

J Mater Chem B 2021 Jun;9(21):4412

Tianjin Key Laboratory of Biomaterial Research Institute of Biomedical Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300192, China.

Correction for 'Co-delivery of anionic epitope/CpG vaccine and IDO inhibitor by self-assembled cationic liposomes for combination melanoma immunotherapy' by Qi Su et al., J. Mater. Chem. B, 2021, 9, 3892-3899, DOI: 10.1039/d1tb00256b.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d1tb90081aDOI Listing
June 2021

Co-delivery of anionic epitope/CpG vaccine and IDO inhibitor by self-assembled cationic liposomes for combination melanoma immunotherapy.

J Mater Chem B 2021 05;9(18):3892-3899

Tianjin Key Laboratory of Biomaterial Research Institute of Biomedical Engineering Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300192, China.

Immunotherapy is revolutionizing cancer treatment. Vaccination of antigenic peptides has been identified as a promising strategy for cancer immunotherapy while insufficient immune responses were stimulated due to low antigenicity. Moreover, immune checkpoint blockade therapy is still limited by a low objective response rate. In this work, cationic polymer-lipid hybrid nanovesicle (P/LNV)-based liposomes are designed to simultaneously deliver tumor vaccines composed of anionic antigen epitopes, toll-like receptor-9 agonist (TLR9), CpG (AE/CpG), and indoleamine-2,3-dioxygenase (IDO) inhibitor, 1-methyl-tryptophan (1-MT), to increase the immunogenicity of peptide antigens and meanwhile block the immune checkpoint. P/LNV liposomes efficiently enhanced the uptake of vaccines by dendritic cells (DCs) and improved the maturation of DCs indicated by the significantly increased percentage of CD86+MHCI+ DCs, resulting in a potent cytotoxic T-lymphocyte (CTL) response against B16-OVA tumor cells in vitro. Importantly, the combination immunotherapy showed significantly higher therapeutic efficiency towards melanoma tumors in mice, compared with an untreated or individual therapy modality. Mechanistically, the co-delivery system could elicit a strong cancer-specific T-cell response, as characterized by the remarkably increased infiltration of CD8+ T cells in the tumor and draining lymph nodes. Altogether, cationic liposomes delivered with tumor vaccines and IDO inhibitor provide a promising platform for cancer immunotherapy by provoking antitumor T-cell immunity and simultaneously reversing the immunosuppressive tumor microenvironment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d1tb00256bDOI Listing
May 2021

On-demand pH-sensitive surface charge-switchable polymeric micelles for targeting Pseudomonas aeruginosa biofilms development.

J Nanobiotechnology 2021 Apr 9;19(1):99. Epub 2021 Apr 9.

School of Pharmacy, Shandong New Drug Loading & Release Technology and Preparation Engineering Laboratory, Binzhou Medical University, 346 Guanhai Road, Yantai, 264003, People's Republic of China.

Bacterial biofilm is the complicated clinical issues, which usually results in bacterial resistance and reduce the therapeutic efficacy of antibiotics. Although micelles have been drawn attention in treatment of the biofilms, the micelles effectively permeate and retain in biofilms still facing a big challenge. In this study, we fabricated on-demand pH-sensitive surface charge-switchable azithromycin (AZM)-encapsulated micelles (denoted as AZM-SCSMs), aiming to act as therapeutic agent for treating Pseudomonas aeruginosa (P. aeruginosa) biofilms. The AZM-SCSMs was composed of poly(L-lactide)-polyetherimide-hyd-methoxy polyethylene glycol (PLA-PEI-hyd-mPEG). It was noteworthy that the pH-sensitive acylhydrazone bond could be cleaved in acidic biofilm microenvironment, releasing the secondary AZM-loaded cationic micelles based on PLA-PEI (AZM-SCMs) without destroying the micellar integrity, which could tailor drug-bacterium interaction using micelles through electrostatic attraction. The results proved that positively charged AZM-SCMs could facilitate the enhanced penetration and retention inside biofilms, improved binding affinity with bacterial membrane, and added drug internalization, thus characterized as potential anti-biofilm agent. The excellent in vivo therapeutic performance of AZM-SCSMs was confirmed by the targeting delivery to the infected tissue and reduced bacterial burden in the abscess-bearing mice model. This study not only developed a novel method for construction non-depolymerized pH-sensitive SCSMs, but also provided an effective means for the treatment of biofilm-related infections.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12951-021-00845-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034112PMC
April 2021

pH-Sensitive Polycations for siRNA Delivery: Effect of Asymmetric Structures of Tertiary Amine Groups.

Macromol Biosci 2021 05 26;21(5):e2100025. Epub 2021 Mar 26.

School of Pharmacy, Shandong New Drug Loading & Release Technology and Preparation Engineering Laboratory, Binzhou Medical University, Yantai, 264003, China.

pH-sensitive polyelectrolytes provide enormous opportunity for siRNA delivery. Especially, their tertiary amine structures can not only bind genes but also act as pH-sensitive hydrophobic structure to control genes release. However, the influence of molecular structures on siRNA delivery still remains elusive, especially for the asymmetric alkyl substituents of the tertiary amine groups. Herein, a library of N-methyl-N-alkyl aminoethyl methacrylate monomers (MsAM) with asymmetric alkyl substituents on the tertiary amine group is synthesized and used to prepare a series of tri-block polycationic copolymers poly(aminoethyl methacrylate)-block-poly (N-methyl-N-alkyl aminoethyl methacrylate)-block-poly(ethylene glycol methacrylate) (PAMA-PMsMA-PEG). And the properties of these polycations and their self-assembled micelles are characterized, including molecular structure, proton buffering capacity, pH-sensitivity, size, and zeta potential. With the length increase of one alkyl substituent, the proton buffering capacity of both monomers and polycations is demonstrated to be narrowed down. The siRNA delivery efficiency and cytotoxicity of these micelles are also evaluated on HepG2 cells. In particular, poly(aminoethyl methacrylate)-block-poly(N-methyl-N-ethyl aminoethyl methacrylate)-block-poly(ethylene glycol methacrylate) (PAMA-PMEMA-PEG) elicited the best luciferase knockdown efficiency and low cytotoxicity. Besides, PAMA-PMEMA-PEG/siRRM2 also induced significant anti-tumor activity in vitro. These results indicated PAMA-PMEMA-PEG has potential for further use in the design of gene vehicles with the improved efficiency of siRNA delivery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/mabi.202100025DOI Listing
May 2021

Amphiphilic Janus nanoparticles for imaging-guided synergistic chemo-photothermal hepatocellular carcinoma therapy in the second near-infrared window.

Nanoscale 2021 Feb;13(7):3974-3982

Department of Chemistry, Northeast Normal University, 5268 Renmin Street, Changchun, Jilin 130024, P. R. China.

Hepatocellular carcinoma (HCC) is one of the most common and deadly malignant tumors worldwide. With unsatisfactory effects of traditional systematic chemotherapy for HCC owing to its drug resistance, novel therapeutic strategies based on nanomaterials for HCC treatments are promising solutions. To solve the challenges of nanoparticles (NPs)-based drug delivery systems for potential clinical applications, we designed water soluble amphiphilic oleic acid-NaYF4:Yb,Er/polydopamine Au nanoflower Janus NPs (OA-UCNPs/PDA-AuF JNPs) with discrete multi compartment nanostructures as dual-drug delivery systems (DDDSs). This unique nanostructure meets the requirements for containing hydrophobic hydroxycamptothecin/hydrophilic doxorubicin in divided spaces and releasing each drug from non-interfering channels under pH/near-infrared (NIR) dual-stimuli. The amphiphilic DDDSs were utilized to eradicate the tumor burden on a high-fidelity HCC model of a patient-derived xenograft (PDX), and represented an efficient strategy for defeating HCC using multi-modal imaging-guided dual-drug chemo-photothermal therapy in the second NIR window. In addition, the potential mechanisms of action for the DDDSs were evaluated.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d0nr09017dDOI Listing
February 2021

Citric acid inhibits Cd uptake by improving the preferential transport of Mn and triggering the defense response of amino acids in grains.

Ecotoxicol Environ Saf 2021 Mar 25;211:111921. Epub 2021 Jan 25.

Key Laboratory of Original Agro-Environmental Pollution Prevention and Control, Agro-Environmental Protection Institute, Ministry of Agriculture and Rural Affairs, P.R. China, Tianjin 300191, China. Electronic address:

Citric acid (CA) can regulate the balance of anions and cations in plants, and improve their resistance to heavy metals. It is not clear if foliar application with CA has any effect on migration of Cd and Mn in rice plant. In this work, a low-Cd-accumulating indica rice line (P7) and a high-Cd-accumulating line (HZ) were used to investigate the influence of CA on the transport of Cd and Mn as well as amino acid metabolism in grains. Content of Cd in grains and other organs increased with the increase of Cd content (0.1-2.4 mg kg) in soil, while decreased with the foliar application with CA. With the increase of Cd content in rice grains, the content of most amino acids in HZ, P7, HZ+CA and P7 + CA showed an obvious decline trend. Foliar application with CA efficiently raised the Mn:Cd ratio in grains and nodes of both HZ and P7. Meanwhile, the expression levels of OsNramp2, 3 and 5 in panicles were efficiently enhanced by CA application when plants grew in soil with Cd content of 0.6-2.4 mg kg. The increasing effect of CA on the content of 4 amino acids (i.e., Glu, Phe, Thr and Ala) in grains was related to varieties and Cd pollution. These results indicate that foliar application with CA can regulate the transport of Cd and Mn in the opposite directions in tissues and inhibit Cd accumulation in grains by enhancing expression of OsNRAMP 2, 3 or 5 and triggering the defense response of some amino acids in Cd-contaminated environment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ecoenv.2021.111921DOI Listing
March 2021

Harnessing pH-Sensitive Polycation Vehicles for the Efficient siRNA Delivery.

ACS Appl Mater Interfaces 2021 Jan 6;13(2):2218-2229. Epub 2021 Jan 6.

College of Pharmacy, Xinxiang Medical University, 453003 Xinxiang, P.R. China.

pH-sensitive hydrophobic segments have been certificated to facilitate siRNA delivery efficiency of amphiphilic polycation vehicles. However, optimal design concepts for these vehicles remain unclear. Herein, by studying the library of amphiphilic polycations mPEG-PAMA-P(DEA--D5A) (EAE5), we concluded a multifactor matching concept (p values, "proton buffering capacities" (BCs), and critical micelle concentrations (CMCs)) for polycation vehicles to improve siRNA delivery efficiency and . We identified that the stronger BCs in a pH 5.5-7.4 subset induced by EAE5 (p = 6.79) and EAE5 (p = 6.20) are effective for siRNA delivery . Further, the stronger BCs occurred in a narrow subset of pH 5.5-6.5 and the lower CMC attributed to higher siRNA delivery capacity of EAE5 than EAE5 after intravenous administration and subcutaneous injection. More importantly, 87.2% gene knockdown efficacy was achieved by EAE5 subcutaneous injection, which might be useful for an mRNA vaccine adjuvant. Furthermore, EAE5 also successfully delivered siRRM2 to tumor intravenous administration and received highly efficient antitumor activity. Taken together, the suitable p values, strong BCs occurred in pH 5.5-6.5, and low CMCs were probably the potential solution for designing efficient polycationic vehicles for siRNA delivery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsami.0c17866DOI Listing
January 2021

Polymer-lipid hybrid nanovesicle-enabled combination of immunogenic chemotherapy and RNAi-mediated PD-L1 knockdown elicits antitumor immunity against melanoma.

Biomaterials 2021 01 26;268:120579. Epub 2020 Nov 26.

Tianjin Key Laboratory of Biomaterial Research, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, 300192, China. Electronic address:

Immunotherapy has revolutionized cancer treatment; however, only a limited portion of patients show responses to currently available immunotherapy regimens. Here, we demonstrate that RNA interference (RNAi) combined with immunogenic chemotherapy can elicit potent antitumor immunity against melanoma. Specially, we developed cationic polymer-lipid hybrid nanovesicles (P/LNVs) as a new delivery system for doxorubicin and small interfering RNA (siRNA) with extensive cytotoxicity and gene silencing efficiency towards B16 cells. The deployment of doxorubicin-loaded P/LNVs augmented the expression and presentation of endogenous tumor antigens directly in situ by inducing the immunogenic cell death of B16 cells through poly(ADP-ribose) polymerase 1-dependent (PARP1) apoptosis pathway; thereby, eliciting remarkable antitumor immune responses in mice. Leveraging dying B16 cells as a vaccination strategy in combination with RNAi-based programmed cell death ligand 1 (PD-L1) knockdown showed efficacy in both prophylactic and metastasis melanoma settings. Strikingly, PD-L1 blockade synergized with a sub-therapeutic dose of doxorubicin triggered robust therapeutic antitumor T-cell responses and eradicated pre-established tumors in 30% of mice bearing B16 melanoma. Our findings indicated that this combination treatment provided a new powerful immunotherapy modality, characterized by markedly increased infiltration of effector CD8 T cells and effective alleviation of the immunosuppressive microenvironment in tumors. P/LNVs is a versatile and highly scalable carrier that can enable a broad combination of nanomedicine and RNAi, providing new therapeutic strategies for advanced cancers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.biomaterials.2020.120579DOI Listing
January 2021

Combating drug-resistant bacterial infection using biodegradable nanoparticles assembled from comb-like polycarbonates grafted with amphiphilic polyquaternium.

J Mater Chem B 2021 01;9(2):357-365

Department of Polymer Science and Technology, Key Laboratory of Systems Bioengineering of the Ministry of Education, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China. and Tianjin Key Laboratory of Biomaterial Research Institute of Biomedical Engineering Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300192, China and Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300072, China.

Bacterial infection is a serious clinical threat. The misuse of antibiotics has already resulted in the emergence of antibiotic-resistant strains of pathogenic bacteria. Efficient membrane-destructive antibacterial agents are considered as an alternative, promising solution against bacterial infection. Herein, we prepared a new type of comb-like cationic, polyethylene glycol (PEG) block polycarbonates with polyquaternium arms (G-CgQAs). The amphiphilic G-CgQAs could self-assemble into about 60 nm sized nanoparticles (NPs) with positive charges (20~30 mV). G-CgQA-3 NPs with an appropriate hydrophobic-hydrophilic balance in the polyquaternium arms showed antibacterial activity against Gram-negative, Gram-positive, and drug-resistant strains at low concentrations (MIC 64-128 μg mL-1) and low hemolysis (HC50 > 2000 μg mL-1). In vivo anti-infection tests indicated G-CgQA-3 NPs could highly inhibit the growth of vancomycin-resistant bacteria by spraying on wounds. Collectively, G-CgQA NPs hold great promise for the prevention of infection, serving as new antibacterial agents. This study also highlights the significance of a hydrophobic block in positive polyquaternium arms to facilitate the antibacterial activity of cationic, quaternized polymers. The design of comb-like amphiphilic cationic polycarbonates provides a new method for manufacturing antibacterial nano-agents.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d0tb02233kDOI Listing
January 2021

Screening and Matching Amphiphilic Cationic Polymers for Efficient Antibiosis.

Biomacromolecules 2020 12 23;21(12):5269-5281. Epub 2020 Nov 23.

Department of Polymer Science and Technology, Key Laboratory of Systems Bioengineering of the Ministry of Education, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China.

The amphiphilic cationic polymers that mimic antimicrobial peptides have received increasing attention due to their excellent antibacterial activity. However, the relationship between the structure of cationic polymers and its antibacterial effect remains unclear. In our current work, a series of PEG blocked amphiphilic cationic polymers composed of hydrophobic alkyl-modified and quaternary ammonium salt (QAS) moieties have been prepared. The structure-antibacterial activity relationship of these cationic polymers was investigated against and , including PEGylation, random structure, molecular weights, and the content and lengths of the hydrophobic alkyl side chains. The results indicated that PEGylated random amphiphilic cationic copolymer (mPB/T) showed stronger antibacterial activity and better biocompatibility than the random copolymer without PEG (PB/T). Furthermore, mPB/T with appropriate mole fraction of alkyl side chains ( = 0.38), degree of polymerization (DP = 92), and four-carbon hydrophobic alkyl moieties was found to have the optimal structure that revealed the best antibacterial activities against both (MIC = 8 μg/mL, selectivity > 250) and (MIC = 4 μg/mL, selectivity > 500). More importantly, mPB/T could effectively eradicate biofilms by killing the bacteria embedded in the biofilms. Therefore, the structure of mPB/T provided valuable information for improving the antibacterial activity of cationic polymers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.biomac.0c01330DOI Listing
December 2020

An injectable thermosensitive hydrogel self-supported by nanoparticles of PEGylated amino-modified PCL for enhanced local tumor chemotherapy.

Soft Matter 2020 Jun;16(24):5750-5758

Department of Polymer Science and Technology and Key Laboratory of Systems Bioengineering of the Ministry of Education, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China. and Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300072, China.

We synthesized amino-modified poly(ε-caprolactone) PCN-b-PEG-b-PCN (PECN) triblock copolymers and studied the contribution of the introduced amino groups to the drug delivery efficiency of PECN nanoparticles (NPs) and their injectable thermosensitive hydrogels. PECN15 with an optimal amino group content was obtained. Firstly, the hydrophobic drug paclitaxel (PTX) was loaded into PECN15 up to 5.91% and formed PTX/PECN NPs 90 nm in size and with a slightly positive charge (7.3 mV). Furthermore, the injectable PTX/PECN NPs aqueous solution (25 wt%) at ambient temperature could undergo fast gelation at 37 °C and sustainedly release PTX/PECN NPs in 10 days. More importantly, compared with our previously reported PECT NPs, the PECN NPs without an increase in toxicity could improve the cell uptake and enhance intracellular drug release by responding to the acidic environment of the endosome. Thus, the PTX/PECN NPs presented a lower IC50 of 3.14 μg mL-1 than that of the PTX/PECT NPs (7.67 μg mL-1) and free PTX (4.65 μg mL-1). Moreover, through peritumoral injection, the PTX/PECNGel showed 94.27% inhibition rate of tumor growth on day 19, higher than PTX/PECTGel (72.28%) and Taxol® (47.03%). Therefore, the PECN NPs hydrogel provided a more effective injectable platform to enhance local cancer chemotherapy, and also provided the possibility of further functionalization by the reactive amino groups.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d0sm00147cDOI Listing
June 2020

Comb-Like Amphiphilic Polycarbonates with Different Lengths of Cationic Branches for Enhanced siRNA Delivery.

Macromol Biosci 2020 07 13;20(7):e2000143. Epub 2020 May 13.

Department of Polymer Science and Technology, Key Laboratory of Systems Bioengineering of the Ministry of Education, School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300072, China.

Owing to the biodegradability and good biocompatibility polycarbonates show the versatile class of applications in biomedical fields. While their poor functional ability seriously limited the development of functional polycarbonates. Herein, a new Br-containing cyclic carbonate (MTC-Br) and a polycarbonate atom transfer radical polymerization (ATRP) macro-initiator (PEG-PMTC-Br) is synthesized. Then, by initiating the side-chain ATRP of 2-(dimethyl amino)ethyl methacrylate (DMAEMA) on PEG-PMTC-Br, a series of comb-like amphiphilic cationic polycarbonates, PEG-b-(PMTC-g-PDMAEMA) (GMDMs), with different lengths of cationic branches are successfully prepared. All these poly(ethylene glycol)-b-(poly((5-methyl-2-oxo-1,3-dioxane-5-yl) methyl 2-bromo-2-methylpropanoate/1,3-dioxane-2-one)-g-poly(2-dimethyl aminoethyl methacrylate) (GMDMs) self-assembled nanoparticles (NPs) (≈180 nm, +40 mV) can well bind siRNA to form GMDM/siRNA NPs. The gene silence efficiency of GMDM/siRNA high to 80%, which is even higher than the commercial transfection reagent lipo2000 (76%). But GMDM/siRNA shows lower cell uptake than lipo2000. So, the high gene silence ability of GMDM/siRNA NPs can be attributed to the strong intracellular siRNA trafficking capacity. Therefore, GMDM NPs are potential siRNA vectors and the successful preparation of comb-like polycarbonates also provides a facile way for diverse side-chain functional polycarbonates, expanding the application of polycarbonates.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/mabi.202000143DOI Listing
July 2020

Burkholderia sp. Y4 inhibits cadmium accumulation in rice by increasing essential nutrient uptake and preferentially absorbing cadmium.

Chemosphere 2020 Aug 24;252:126603. Epub 2020 Mar 24.

Agro-Environmental Protection Institute, Ministry of Agriculture and Rural Affairs, Tianjin, 300191, People's Republic of China. Electronic address:

Microbial remediation of heavy metal-polluted soil is a commonly used method. Burkholderia sp. Y4, isolated from cadmium (Cd)-contaminated rice rhizosphere soil, was investigated for its direct and indirect effects on Cd accumulation in rice by SEM-EDS, FITR and sequencing analysis of the soil bacterial community. Burkholderia sp. Y4 inoculation reduced Cd accumulation in rice roots, rachises, and grains of the two rice varieties T705 and X24 and increased levels of essential elements, especially Fe and Mn, which competitively inhibited Cd transport through cationic channels. Living Burkholderia sp. Y4 cells, rather than non-living ones, could colonize the surface of rice roots and accumulated more Cd through direct biosorption associated with -CO and -NH/-CO bonds of amino acids and proteins. The results of soil microbial community showed that the colonization of externally added Burkholderia sp. Y4 could be maintained over some time to impact the total rhizospheric environment. Burkholderia sp. Y4 inoculation decreased the abundance of microbes involved in the iron cycle (Acidobacteria) as well as of those mediating the transformation of ammonium nitrogen to nitrate nitrogen (Nitrosomonadaceae and Nitrospira). So Burkholderia sp. Y4 inoculation may indirectly change the availability of micronutrients and Cd in rice rhizosphere soil through iron-nitrogen coupled cycles to increase essential nutrient uptake and inhibit Cd accumulation in rice by preferential Cd-biosorption. Therefore, Burkholderia sp. Y4 is potentially suitable for the bioremediation of Cd-contaminated paddy soil.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.chemosphere.2020.126603DOI Listing
August 2020

Rice grains alleviate cadmium toxicity by expending glutamate and increasing manganese in the cadmium contaminated farmland.

Environ Pollut 2020 Jul 26;262:114236. Epub 2020 Feb 26.

Key Laboratory of Original Agro-Environmental Pollution Prevention and Control, Agro-Environmental Protection Institute, Ministry of Agriculture and Rural Affairs, PR China, Tianjin 300191, China. Electronic address:

The accumulation of cadmium (Cd) in rice grains is closely associated with the content of mineral nutrients and amino acid metabolism, but the causal link among them is unclear. Profiles of amino acids (AAs) and quantities of essential nutrients in grains from early and late rice cultivars grown at four sites with different Cd levels were analyzed in the present study. Hazard quotients (HQs) for consumers by intake of rice from late cultivars were much higher than that from early cultivars at sites with soil Cd content of 0.25, 0.61 and 0.84 mg kg. Cadmium accumulation in grains resulted in a sharp reduction of total essential AAs and non-essential AAs in both early and late rice cultivars. High-Cd-accumulating (HCA) cultivars had significantly higher level of glutamate (Glu) than low-Cd-accumulating (LCA) cultivars when rice Cd content was less than 0.20 mg kg. However, Glu level in grains dramatically declined with the accumulation of Cd, which subsequently leaded to the reduction of other AAs. Cadmium content was well predicted by five amino acids (i.e., Glu, Alanine, Phenylalanine, Glycine and Threonine) or four essential elements (Ca, Fe, Mn and Zn) when rice Cd was less than 0.80 mg kg. Amino acids played more important roles than nutrients in Cd accumulation. When Cd content was in the range of 0.40-1.16 mg kg, the Mn content in rice increased significantly with the increase of Cd content, while the Glu content dropped down synchronously. Remarkably, the ratio between Mn and Glu displayed the highest direct path coefficient on Cd accumulation than any single cation or amino acid. These results indicate that high capacity in synthesizing Glu and concentrating Mn is the determinant factor for Cd accumulation in rice grains, and abundant Glu in aleurone layer may alleviate Cd toxicity by forming Glu-Cd complex.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.envpol.2020.114236DOI Listing
July 2020

"Off/on" fluorescence imaging-guided cancer diagnosis and multi-modal therapy.

Biomater Sci 2020 Mar 21;8(5):1442-1454. Epub 2020 Jan 21.

Department of Polymer Science and Technology, School of Chemical Engineering and Technology, Key Laboratory of Systems Bioengineering of the Ministry of Education, Tianjin University, Tianjin 300072, China.

An efficient theranostic nanoplatform responding to tumour microenvironments with characters of simple and flexible combinations owns great potential in cancer diagnosis and therapy. Herein, a series of triblock copolymers, mPEG-b-PDPA-b-P(nBMA-r-cystamine) (EPB), were synthesized and among them, the structure of EPB-3 was optimized for both fluorescence imaging-guided cancer diagnosis and multi-modal therapy with good biocompatibility. (1) The self-assembled nanoparticles of EPB-3-ICG obtained by conjugating one ICG on EPB-3 via S-S bonds effectively performed reduction-sensitive OFF/ON fluorescence signal transition, thus inducing tumour cell-specific amplified fluorescence imaging in vitro and in vivo. (2) By entrapping Au nanorods into the co-assembled NPs of EPB-3 and EPB-3-ICG, [email protected] NPs could synchronously induce strong tumour fluorescence imaging and high local photothermal effect, indicating the potential of imagine-guided photothermal therapy. (3) EPB-3 NPs could efficiently co-load paclitaxel (PTX) and ICG to form stable [email protected]@ICG NPs, which provided long periods of intracellular pH-sensitive sustainable drug release and highly enhanced apoptosis of 4T1 cells in vitro by the chemo-photothermal effect. Excitingly, a single intravenous injection of [email protected]@ICG NPs followed by a one-time local near-infrared light (NIR, 808 nm) irradiation treatment for 10 min could lead to significant inhibition of tumour growth, avoiding tumor metastasis and extending the survival of mice. All the above-mentioned results suggest that EPB-3 provides a nanoplatform with the characters of simple structure, convenience of use and flexible combination, holding potential for multi-modal diagnosis and therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/c9bm01854aDOI Listing
March 2020

Co-localized delivery of nanomedicine and nanovaccine augments the postoperative cancer immunotherapy by amplifying T-cell responses.

Biomaterials 2020 02 22;230:119649. Epub 2019 Nov 22.

Tianjin Key Laboratory of Biomaterial Research, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, 300192, China. Electronic address:

Immunotherapy in solid tumors is limited by the poor immunogenicity of tumors and limited T-cell immune response, resulting in low patient response rate. To increase the efficiency of cancer immunotherapy, a unique synergistic combination cancer immunotherapy by co-localized delivery of cancer nanomedicine for enhancing the tumor immunogenicity and nanovaccine for augmenting the antitumor T-cell immunity was developed for post-surgical tumor treatment. The thermo-responsive, curcumin-loaded polymer nanoparticles (nanomedicine)-assembled hydrogel enabled the complete coverage of the surgical bed of primary tumor and the spatio-temporal delivery of cognate nanomedicines and encapsulated nanovaccines. Importantly, the nanomedicine efficiently induced the immunogenic cell death (ICD) of residual cancer cells, and consequently enhanced the tumor immunogenicity and sensitized the tumor to antitumor T-cell immunity. The cancer nanovaccine composed of antigenic peptide, CpG-ODN and cationic polymer nanoparticle significantly triggered the maturation of dendritic cells (DCs) and elicited potent vaccine-specific T-cell immune responses. Using highly malignant postoperative breast carcinoma 4T1 models, we found that the combination immunotherapy strategy strikingly amplified the level of systemic host T-cell immunity, promoted the infiltration of CD8 T lymphocytes in tumor, and thus efficaciously attenuated the local tumor recurrence and pulmonary metastasis. Collectively, this work provided an advanced synergistic combination approach for post-surgical tumor immunotherapy. The self-assembled hydrogel should enable a broader combination of immunomodulating nanomedicines and vaccines for cancer immunotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.biomaterials.2019.119649DOI Listing
February 2020

Increasing phosphate inhibits cadmium uptake in plants and promotes synthesis of amino acids in grains of rice.

Environ Pollut 2020 Feb 31;257:113496. Epub 2019 Oct 31.

Key Laboratory of Original Agro-Environmental Pollution Prevention and Control, Agro-Environmental Protection Institute, Ministry of Agriculture and Rural Affairs, Tianjin 300191, China. Electronic address:

Technologies for cleaner production of rice in cadmium (Cd) contaminated field are being explored worldwide. In order to investigate the inhibition mechanism of phosphate on Cd transport in soil-plant system, controlled experiments were performed in this study. Experimental results showed that Cd levels in roots, flag leaves, rachises and grains of rice plants (Oryza sativa L.) were significantly reduced by supplement of 0.5-2.5 g kg calcium magnesium phosphate fertilizer (CMP). Path coefficient analysis revealed that phosphorous had significant negative direct effect on Cd, but positive indirect effect on essential and non-essential amino acids. Applying 2.5 g kg CMP made the Cd concentration decreased by 45.7% while free essential and non-essential amino acids increased by 28.0-28.6% in grains. Levels of the branched-chain amino acids in grains were much higher than other essential amino acids, and increased with the amount of CMP fertilization. After application of CMP, pH of soil solution and thickness of the iron plaque around roots increased significantly. Spectra from X-ray photoelectron spectrometer (XPS) showed that content of N, P and Fe increased apparently, C, O and Ca had no change, while S decreased by 74.2% in roots after application of 2.5 g kg CMP. Meanwhile, Cd concentration in protoplasts of root cells decreased by 39.5-80.1% with the increase of CMP. These results indicate that application of CMP can effectively inhibit Cd accumulation in root protoplasts by promoting iron plaque formation on the root surface, reduce Cd concentration and increase free amino acids in rice grains.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.envpol.2019.113496DOI Listing
February 2020

Cadmium-resistant rhizobacterium Bacillus cereus M4 promotes the growth and reduces cadmium accumulation in rice (Oryza sativa L.).

Environ Toxicol Pharmacol 2019 Nov 19;72:103265. Epub 2019 Sep 19.

College of Food Science and Biotechnology, Tianjin Agricultural University, Tianjin, 300384, People's Republic of China.

Rice farmland cadmium pollution is an increasing problem for food safety. Cd-resistant bacterial strain was isolated from rice rhizosphere soil and identified as Bacillus cereus M4. Treatment with M4 fermentation broth increased rice seedlings growth in vermiculite, while reduced Cd accumulation in grains of rice grown in Cd-contaminated potted soil from 0.309 to 0.186 mg/kg. Indoleacetic acid (IAA) was detected in M4 metabolites and in potted soil solutions supplemented with M4 broth. M4 broth increased the abundance of Bacillus from 0.54% to 0.95% and changed the soil bacterial community composition. These findings indicate that M4 promotes rice growth by secreting IAA and altering the rhizospheric soil microenvironment, via soil solution composition and microbial community, which may affect Cd translocation from soil to rice roots, thereby decreasing grain Cd accumulation. Therefore, B. cereus M4 is potentially suitable for the bioremediation of Cd-contaminated paddy soils.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.etap.2019.103265DOI Listing
November 2019

Variety-dependent responses of rice plants with differential cadmium accumulating capacity to cadmium telluride quantum dots (CdTe QDs): Cadmium uptake, antioxidative enzyme activity, and gene expression.

Sci Total Environ 2019 Dec 23;697:134083. Epub 2019 Aug 23.

Institute of Environmental Processes and Pollution Control, School of Environmental and Civil Engineering, Jiangnan University, Wuxi 214122, China.

The excess release of engineered nanomaterials into farmland poses a serious threat to food security. Although rice varieties exhibit substantial variation in cadmium accumulation, their responses to Cd-based nanoparticles are largely unknown. In this work, we investigated the accumulation of cadmium telluride quantum dots (CdTe QDs at 0.5, 1.0, 2.5, 5.0mg-Cd/L) in two rice varieties with different Cd accumulation capacity. It was found that 5.0mg-Cd/L of CdTe QDs had minor growth inhibition to the high-Cd-accumulating variety (T705) relative to the low-Cd-accumulating variety (X24) after 7-day exposure. The two rice varieties had comparable Cd content in roots; however, T705 exhibited higher Cd content in shoots than X24. Transmission electron and confocal laser scanning microscopic observations demonstrated that more CdTe QDs can be transported and accumulated from roots to shoots in T705. The activities and gene expression of antioxidative enzymes in leaves of T705 increased more significantly than those of X24. Our findings for the first time validated that Cd accumulation divergence exists in different rice varieties when they are exposed to Cd-based QDs, the genetic basis for which needs to be further examined.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.scitotenv.2019.134083DOI Listing
December 2019

Glutathione-Priming Nanoreactors Enable Fluorophore Core/Shell Transition for Precision Cancer Imaging.

ACS Appl Mater Interfaces 2019 Sep 23;11(37):33667-33675. Epub 2019 Aug 23.

Institute of Systems Biomedicine, Beijing Key Laboratory of Tumor Systems Biology, School of Basic Medical Sciences , Peking University Health Science Center , Beijing 100191 , China.

In an attempt to develop an imaging probe with ultra-high sensitivity for a broad range of tumors in vivo and inspired by the concept of chemical synthetic nanoreactors, we designed a type of glutathione-priming fluorescent nanoreactor (GPN) with an albumin-coating shell and hydrophobic polymer core containing disulfide bonds, protonatable blocks, and indocyanine green (ICG), a near-infrared fluorophore. The albumin played multiple roles including biocompatible carriers, hydrophilic stabilizer, "receptor" of the fluorophores, and even targeting molecules. The protonation of the hydrophobic core triggered the outside-to-core transport of acidic glutathione (GSH), as well as the core-to-shell transference of ICGs after the disulfide bond cleavage by GSH, which induced strong binding of fluorophores with albumins on the GPN shell, initiating intensive fluorescence signals. As a result, the GPNs demonstrated extremely high response sensitivity and imaging contrast, proper time window, and broad cancer specificity. In fact, an orthogonal activation pattern was found in vitro with an ON/OFF ratio up to 24.7-fold. Furthermore, the nanoprobes specifically amplified the tumor signals in five cancer-bearing mouse models and actualized tumor margin delineation with a contrast up to 20-fold, demonstrating much better imaging efficacy than the other four commercially available probes. Therefore, the GPNs provide a new paradigm in developing high-performance bioresponsive nanoprobes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsami.9b11063DOI Listing
September 2019

Efficacy, immunogenicity and safety of the AS04-HPV-16/18 vaccine in Chinese women aged 18-25 years: End-of-study results from a phase II/III, randomised, controlled trial.

Cancer Med 2019 10 15;8(14):6195-6211. Epub 2019 Jul 15.

GSK, Wavre, Belgium.

Background: Cervical cancer is a major public health concern in China. We report the end-of-study results of a phase II/III trial to assess the efficacy, immunogenicity, and safety of the AS04-human papillomavirus (HPV)-16/18 vaccine in Chinese women aged 18-25 years followed for up to 72 months after first vaccination. Results of approximately 57 months following first vaccination have been previously reported.

Methods: Healthy 18-25-year-old women (N = 6051) were randomized (1:1) to receive three doses of AS04-HPV-16/18 vaccine or Al(OH) (control) at Months 0-1-6. Vaccine efficacy against HPV-16/18 infection and cervical intraepithelial neoplasia (CIN), cross-protective vaccine efficacy against infections and lesions associated with nonvaccine oncogenic HPV types, immunogenicity, and safety were assessed. Efficacy was assessed in the according-to-protocol efficacy (ATP-E) cohort (vaccine N = 2888; control N = 2892), total vaccinated cohort for efficacy (TVC-E; vaccine N = 2987; control N = 2985) and TVC-naïve (vaccine N = 1660; control N = 1587).

Results: In initially HPV-16/18 seronegative/DNA-negative women, vaccine efficacy against HPV-16/18-associated CIN grade 2 or worse was 87.3% (95% CI: 5.5, 99.7) in the ATP-E, 88.7% (95% CI: 18.5, 99.7) in the TVC-E, and 100% (95% CI: 17.9, 100) in the TVC-naïve. Cross-protective efficacy against incident infection with HPV-31, HPV-33 and HPV-45 was 59.6% (95% CI: 39.4, 73.5), 42.7% (95% CI: 15.6, 61.6), and 54.8% (95% CI: 19.3, 75.6), respectively (ATP-E). At Month 72, >95% of initially seronegative women who received HPV vaccine in the ATP cohort for immunogenicity (N = 664) remained seropositive for anti-HPV-16/18 antibodies; anti-HPV-16 and anti-HPV-18 geometric mean titers were 678.1 EU/mL (95% CI: 552.9, 831.5) and 343.7 EU/mL (95% CI: 291.9, 404.8), respectively. Serious adverse events were infrequent (1.9% vaccine group [N = 3026]; 2.7% control group [N = 3025]). Three and zero women died in the control group and the vaccine group respectively. New onset autoimmune disease was reported in two women in the vaccine group and two in the control group.

Conclusions: This is the first large-scale randomized clinical trial of HPV vaccination in China. High and sustained vaccine efficacy against HPV-16/18-associated infection and cervical lesions was demonstrated up to Month 72. The vaccine had an acceptable safety profile. Combined with screening, prophylactic HPV vaccination could potentially reduce the high burden of HPV infection and cervical cancer in China.

Trial Registration: NCT00779766.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cam4.2399DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6797633PMC
October 2019

Gadolinium inhibits cadmium transport by blocking non-selective cation channels in rice seedlings.

Ecotoxicol Environ Saf 2019 Sep 28;179:160-166. Epub 2019 Apr 28.

Key Laboratory of Original Agro-Environmental Pollution Prevention and Control, Agro-Environmental Protection Institute, Ministry of Agriculture and Rural Affairs, PR China, Tianjin, 300191, China. Electronic address:

Non-selective cation channels (NSCCs) play important roles in uptake of heavy metals in plants. However, little information is available concerning the contribution of NSCCs to cadmium (Cd) transport in rice seedlings. Results from the hydroponic experiment showed that the inhibition of 2.7 μM Cd on the development of rice roots was alleviated by adding 0.1 mM gadolinium (Gd) in nutrient solution, companied by reduction of Cd content by 55.3% in roots and by 45.0% in shoots. Inhibition of Gd on Cd accumulation in cytoplasm fraction (F3) was much greater than that in cell walls (F1) and organelles (F2) in roots. After increasing concentrations of Mn and Zn in nutrient solution, adding 0.1 mM Gd resulted in reductions in Cd content by 89.1%, in micronutrients by 54.9% and in macronutrients by 5.4% in roots, respectively. Cd stress resulted in significant increase of PC and free amino acids, but decrease of V-ATPase activity by 32.3% in roots. These results indicate that NSCCs make a great contribution to uptake of Cd in rice seedlings and opportunities for Cd to be transported by NSCCs can be efficiently reduced by blocking NSCCs and/or increasing essential microelements like Mn and Zn.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ecoenv.2019.04.057DOI Listing
September 2019

Structural exploration of hydrophobic core in polycationic micelles for improving siRNA delivery efficiency and cell viability.

J Mater Chem B 2019 02 21;7(6):965-973. Epub 2019 Jan 21.

Department of Polymer Science and Technology, School of Chemical Engineering and Technology, Key Laboratory of Systems Bioengineering (Ministry of Education), Tianjin University, Tianjin 300072, China.

Improving siRNA delivery efficiency often encounters a dilemma with poor or decreased biocompatibility for polycationic micelles. To address this dilemma, this work focused on a structural exploration of the hydrophobic core in amphiphilic polycationic micelles by preparing two amphiphilic polycations with block or random hydrophobic segments, poly(ethylene glycol)-block-poly(aminoethyl methacrylate)-block-poly(2-diamylamine ethyl methacrylate)-block-poly(2-diethylamine ethyl methacrylate) (mPEG-PAMA-PD5A-PDEA, PADE) and poly(ethylene glycol)-block-poly(aminoethyl methacrylate)-block-poly(2-diamylamine ethyl methacrylate-co-2-diethylamine ethyl methacrylate) (mPEG-PAMA-P(D5A/DEA), PA(D/E)). The properties of the two copolymers and their self-assembly micelles were characterized, including structure, morphology, size and zeta potential. Cytotoxicity, siRNA silencing efficiency and cellular uptake of PADE/siRNA and PA(D/E)/siRNA complexes were evaluated in HepG2 and MDA-MB-231 cells in vitro. The endosome escape and intracellular distribution of PADE/siRNA and PA(D/E)/siRNA in HepG2 cells were also observed by CLSM. Significantly, the results indicated that PA(D/E)/siRNA showed not only better gene silencing efficiency but also lower cytotoxicity, which may be attributed to the homogeneous morphology of the hydrophobic core of PA(D/E) micelles. Therefore, this work provides a new pathway to overcome the dilemma between siRNA delivery efficiency and biocompatibility for the development of efficient polycation carriers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/c8tb02706dDOI Listing
February 2019

The study of relationships between pKa value and siRNA delivery efficiency based on tri-block copolymers.

Biomaterials 2018 09 29;176:84-93. Epub 2018 May 29.

Laboratory of Nucleic Acid Technology, Institute of Molecular Medicine, Peking University, Beijing, 100871, China. Electronic address:

Tri-block copolymers have exhibited great potentials in small interfering RNA (siRNA) therapeutics. To reveal structure-activity relationships, we here synthesized a series of tri-block copolymers with different hydrophobic segments, PEG-PAMA-P(C6A-C7A-DPA-DBA) (EAAS) and PEG-PDAMAEMA-P(C6A-C7A-DPA-DBA) (EDAS), termed from EAASa to EAASh and EDASa to EDASh, with pKa ranging from 5.2 to 7.0. Our data showed that the better gene silencing efficiency was located in pKa of 5.8-6.2, which was contributed from higher endosomal escape observed with confocal images and hemolysis assay. EAASc, the leader polymer, showed excellent gene knockdown at w/w ratio of 14.5 on HepG2 (89.94%), MDA-MB-231 (92.45%), 293A (83.06%), and Hela cells (80.27%), all better than lipofectamine 2000. Besides, EAASc mediated effective gene silencing in tumor when performed peritumoral injection. This work found out that polymers with pKa ranging from 5.8 to 6.2 were efficient in siRNA delivery, which provided an optimization strategy for siRNA delivery systems, especially for tri-block copolymers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.biomaterials.2018.05.046DOI Listing
September 2018

The pH-Triggered Triblock Nanocarrier Enabled Highly Efficient siRNA Delivery for Cancer Therapy.

Theranostics 2017 11;7(14):3432-3445. Epub 2017 Aug 11.

Laboratory of Nucleic Acid Technology, Institute of Molecular Medicine, Peking University, Beijing 100871, China.

Small interfering RNA (siRNA) therapies have been hampered by lack of delivery systems in the past decades. Nowadays, a few promising vehicles for siRNA delivery have been developed and it is gradually revealed that enhancing siRNA release from endosomes into cytosol is a very important factor for successful delivery. Here, we designed a novel pH-sensitive nanomicelle, PEG-PTTMA-P(GMA-S-DMA) (PTMS), for siRNA delivery. Owing to rapid hydrolysis in acidic environment, PTMS NPs underwent hydrophobic-to-hydrophilic transition in endosomes that enabled combination of proton sponge effect and raised osmotic pressure in endosomes, resulting in vigorous release of siRNAs from endosomes into cytosol. results demonstrated that PTMS/siRNA complexes exhibited excellent gene silencing effects in several cell lines. Their gene silencing efficiency could reach ~91%, ~87% and ~90% at the N/P ratio of 50/1 in MDA-MB-231, A549 and Hela cells respectively, which were better than that obtained with Lipofectamine 2000. The highly efficient gene silencing was then proven from enhanced siRNA endosomal release, which is mainly attributed to pH-triggered degradation of polymer and acid-accelerated siRNA release. experiments indicated that NPs/siRNA formulation rapidly accumulated in tumor sites after i.v. injection. Tumor growth was effectively inhibited and ~45% gene knockdown efficacy was determined at the siRRM2 dose of 1mg/kg. Meanwhile, no significant toxicity was observed during the whole treatment. We also found that PTMS/siRNA formulations could lead to significant gene silencing effects in liver (~63%) and skin (~80%) when injected by i.v. and s.c., respectively. This research work gives a rational strategy to optimize siRNA delivery systems for tumor treatments.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7150/thno.20297DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5596434PMC
July 2018
-->