Publications by authors named "Zhenzhong Zhang"

231 Publications

Dysfunctional beliefs and attitudes about sleep are associated with regional homogeneity of left inferior occidental gyrus in primary insomnia patients: a preliminary resting state functional magnetic resonance imaging study.

Sleep Med 2021 Feb 24;81:188-193. Epub 2021 Feb 24.

Tongde Hospital of Zhejiang Province, Hangzhou and Mental Health Center of Zhejiang Province, Zhejiang 310012, China. Electronic address:

Background: The neural mechanisms of sleep beliefs and attitudes in primary insomnia (PI) patients at resting state remain unclear. The aim of this study was to investigate the features of regional homogeneity (ReHo) in PI using resting-state functional magnetic resonance imaging (rsfMRI).

Methods: Thirty-two PI patients and 34 normal controls (NC) underwent rsfMRI using a 3 T scanner at Tongde Hospital of Zhejiang Province. Participants were assessed with the Dysfunctional Beliefs and Attitudes about Sleep scale (DBAS-16) and Pittsburgh Sleep Quality Index (PSQI). Statistical analyses were performed to determine the regions in which ReHo differed between the two groups. Correlation analyses were performed between the ReHo index of each of these regions and DBAS-16 in PI patients.

Results: PI patients showed increased ReHo values in the right superior frontal gyrus, and decreased ReHo values in the left cerebellar gyrus, left inferior occipital gyrus (IOG) and left amygdala compared with those of NC. ReHo values in the left IOG were negatively correlated with total DBAS-16 scores, and scores for "consequences of insomnia" and"worry/helplessness about sleep"in PI patients.

Conclusions: These results suggest that ReHo alterations in the left IOG may play an important role in the dysfunctional beliefs and attitudes about sleep in PI.
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http://dx.doi.org/10.1016/j.sleep.2021.02.039DOI Listing
February 2021

Adaptation of life-history traits and trade-offs in marine medaka (Oryzias melastigma) after whole life-cycle exposure to polystyrene microplastics.

J Hazard Mater 2021 Feb 25;414:125537. Epub 2021 Feb 25.

College of Marine Life Sciences, Ocean University of China, 5 Yushan Road, Qingdao 266003, Shandong, China. Electronic address:

Microplastics are ubiquitous in marine environments and may cause unexpected ecological effects. This study adopted a whole life-cycle exposure to illuminate the impact of polystyrene microplastics on life-history strategies of marine medaka (Oryzias melastigma), including the hatching of embryos, growth and reproduction of F generation, and embryonic and larval development of F offspring. Microplastics accumulated on the eggshell and reduced embryonic hatching rate and larval body length and weight. Similarly, 150 days of microplastic exposure decreased body mass and gonadosomatic index of adult fish, but accelerated sexual maturity of female fish, showing a trade-off between growth and reproduction. Microplastic exposure also caused obvious histopathological damages to gonads and decreased egg productions and fertilization rates. Moreover, parental microplastic exposure induced elevated heartbeats, premature hatching, and slow growth in F offspring. Anti-oxidative stress response, sex hormone disruption, and disturbed transcription of steroidogenic genes in the reproductive axis could partially explain the reproduction impairment and transgenerational trade-offs. Furthermore, transcriptome analysis revealed that the steroid hormone biosynthesis and cytochrome P450 pathways in the testes of male fish were significantly affected after 20 μg/L microplastic exposure. These findings suggest that microplastic pollution may be an emerging threat to the sustainability of marine fish population.
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http://dx.doi.org/10.1016/j.jhazmat.2021.125537DOI Listing
February 2021

Pressure-driven accumulation of Mn-doped mesoporous silica nanoparticles containing 5-aza-2-deoxycytidine and docetaxel at tumours with a dry cupping device.

J Drug Target 2021 Mar 3:1-10. Epub 2021 Mar 3.

School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, PR China.

Drug delivery with the help of nanoparticles could transport more payloads to tumour site. Owing to their limited accumulation and penetration in the tumour tissues, to increase delivery efficiency is currently still required for applying nanomedicine to treat tumour. Here, we initially report a pressure-driven accumulation of drug-loaded nanoparticles to tumours for efficient tumour therapy with a dry cupping device. The mesoporous Mn-doped silica based nanoparticles delivering 5-aza-2-deoxycytidine and docetaxel were prepared, characterised and used as a model nanomedicine to investigate the potential of dry cupping treatment. For this system, the Mn doping not only endowed the mesoporous silica nanoparticles biodegradability, but also made it much easier to bind a tumour targeting group, which is a G-quadruplex-forming aptamer AS1411. On tumour-bearing mice, the results demonstrated that the dry cupping treatment could substantially improve the distribution of nanomedicines at tumour site, resulting in enhanced treatment efficacy. Overall, this method enables the therapeutical nanoparticles accumulate to tumour through increasing the blood perfusion as well as altering the biological barrier, which opened up possibilities for the development of pressure-driven nanomedicine accumulation at tumour site.
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http://dx.doi.org/10.1080/1061186X.2021.1892117DOI Listing
March 2021

Biomimetic Nanoscale Erythrocyte Delivery System for Enhancing Chemotherapy via Overcoming Biological Barriers.

ACS Biomater Sci Eng 2021 04 2;7(4):1496-1505. Epub 2021 Mar 2.

School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou 450001, China.

Overcoming multiple biological barriers, including circulation time , tumor vascular endothelium, reticuloendothelial system (RES), extracellular matrix (ECM), etc., is the key to improve the therapeutic efficacy of drug delivery systems in treating tumors. Inspired by the ability of natural erythrocytes to cross multiple barriers, in this study, a biomimetic delivery system named NE@DOX-Ang2 was developed for enhancing the chemotherapy of breast cancer, which employed nano-erythrocyte (NE) encapsulating doxorubicin (DOX) and surface modification with a targeted angiopep-2 peptide (Ang2). NE@DOX-Ang2 enhanced the capacity to cross biological barriers in a three-dimensional (3D) tumor spheroid model and in mice. Compared with a conventional drug delivery system of liposomes, the half-life of NE@DOX-Ang2 increased approximately 2.5 times. Moreover, NE@DOX-Ang2 exhibited excellent tumor-targeting ability and antitumor effects and . Briefly, the prepared nano-erythrocyte drug carrier has features of favorable biocompatibility and low immunogenicity and the advantage of prolonging the half-life of drugs, which may provide a novel perspective for development of clinically available nanomedicines.
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http://dx.doi.org/10.1021/acsbiomaterials.1c00008DOI Listing
April 2021

A revised definition of dynamic adsorption coefficient for characterizing activated carbon instead of retention bed.

J Hazard Mater 2021 May 30;409:124994. Epub 2020 Dec 30.

Environmental Technology Division, Institute of Nuclear and New Energy Technology, Tsinghua University, Beijing 100084, China; Institute of Nuclear and New Energy Technology, Collaborative Innovation Center of Advanced Nuclear Energy Technology, Key Laboratory of Advanced Reactor Engineering and Safety of Ministry of Education, Tsinghua University, Beijing 100084, China. Electronic address:

Activated carbon (AC) retention beds are widely used in nuclear facilities, removing radioactive contaminants from exhaust air. Dynamic adsorption coefficient (DAC) is the core parameter to quantify the performance. Its definition has not been unified and it is affected by the geometry of the retention bed, the presence, the flow rate, and the concentration of adsorbate. So, DAC is currently a parameter characterizing the adsorption performance of the retention bed instead of the AC. In this regard, the definition of DAC should be revised, stripping away the influence of other factors. In this study, a 1D model for the AC column, a 2D model for blank piping, and a mathematical model for retention factor is developed. All are validated with simulations and experiments based on the "pulse dynamic method". They are used to analyze the factors affecting DAC quantitatively in detail, including the direct effect of blank piping, the indirect effect of blank piping by affecting the pulse height into the column, and the effect of krypton concentration distribution in the column. Finally, an improved definition of DAC characterizing AC instead of retention bed is given. This definition can be used as a reference for scholars who formulate relevant standards.
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http://dx.doi.org/10.1016/j.jhazmat.2020.124994DOI Listing
May 2021

Cascade Catalytic Nanoplatform Based on "Butterfly Effect" for Enhanced Immunotherapy.

Adv Healthc Mater 2021 Jan 14:e2002171. Epub 2021 Jan 14.

School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, 450001, P. R. China.

The unique tumor microenvironment (TME) characteristics such as immunosuppression impeded traditional cancer treatments. In contrast, developing cascade catalytic nanoplatforms by fully making use of substances in TME for cancer therapy may deserve full credit. Herein, a cascade catalytic nanoplatform based on glucose oxidase (GOD) modified mesoporous iron oxide nanoparticles (IONP) loaded with Artemisinin (ART) is developed, which is designed as IONP-GOD@ART. GOD can catalyze the oxidization of glucose into gluconic acid and H O , which not only realizes tumor starvation therapy, but also provides H O for IONP mediated Fenton reaction. Simultaneously, mesoporous IONP releases Fe and Fe ions in acidic TME. On the one hand, iron ions undergo Fenton reaction to generate hydroxyl radicals for chemodynamic therapy. On the other hand, the endoperoxide bridge in ART is broken in presence of Fe and further generates reactive oxygen species (ROS) to achieve therapeutic purpose. In this sense, IONP-GOD@ART manipulates TME characteristics and leads to "butterfly effect", which brings out a large amount of ROS for eliciting immunogenic cell death, inducing M1-TAMs polarization, and further reprogramming immunosuppressive TME for enhanced immunotherapy. By this delicate design, the cascade catalytic nanoplatform of IONP-GOD@ART realizes potent cancer immunotherapy for tumor regression and metastasis prevention.
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http://dx.doi.org/10.1002/adhm.202002171DOI Listing
January 2021

Tumor cell-activated "Sustainable ROS Generator" with homogeneous intratumoral distribution property for improved anti-tumor therapy.

Theranostics 2021 1;11(1):379-396. Epub 2021 Jan 1.

School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China.

Photodynamic therapy (PDT) holds a number of advantages for tumor therapy. However, its therapeutic efficiency is limited by non-sustainable reactive oxygen species (ROS) generation and heterogeneous distribution of photosensitizer (PS) in tumor. Herein, a "ustainable OS enerator" (SRG) is developed for efficient antitumor therapy. SRG was prepared by encapsulating small-sized MnO-Ce6 nanoparticles (MC) into dendritic mesoporous silica nanoparticles (DMSNs) and then enveloped with hyaluronic acid (HA). Due to the high concentration of HAase in tumor tissue, the small-sized MC could be released from DMSNs and homogeneously distributed in whole tumor. Then, the released MC would be uptaken by tumor cells and degraded by high levels of intracellular glutathione (GSH), disrupting intracellular redox homeostasis. More importantly, the released Ce6 could efficiently generate singlet oxygen (O) under laser irradiation until the tissue oxygen was exhausted, and the manganese ion (Mn) generated by degraded MC would then convert the low toxic by-product (HO) of PDT to the most harmful ROS (·OH) for sustainable and recyclable ROS generation. MC could be homogeneously distributed in whole tumor and significantly reduced the level of intracellular GSH. At 2 h after PDT, obvious intracellular ROS production was still observed. Moreover, during oxygen recovery in tumor tissue, ·OH could be continuously produced, and the nanosystem could induce 82% of cell death comparing with 30% of cell death induced by free Ce6. For PDT, SRG achieved a complete inhibition on tumor growth. Based on these findings, we conclude that the designed SRG could induce sustainable ROS generation, homogeneous intratumoral distribution and intracellular redox homeostasis disruption, presenting an efficient strategy for enhanced ROS-mediated anti-tumor therapy.
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http://dx.doi.org/10.7150/thno.50028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7681092PMC
January 2021

Acetic acid transporter-mediated, oral, multifunctional polymer liposomes for oral delivery of docetaxel.

Colloids Surf B Biointerfaces 2021 Feb 1;198:111499. Epub 2020 Dec 1.

School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450001, China; Henan Key Laboratory of Targeted Therapy and Diagnosis of Tumor and Major Diseases, Henan Province, Zhengzhou, 450001, China. Electronic address:

Nanoparticle-structuring aimed at the acetic acid (A) transporter on intestinal epithelial cells and tumor cells is a new potential strategy to enhance oral bioavailability and anti-tumor efficacy. In this study, chitosan (CS) was modified with hydrophilic A and hydrophobic lipoic acid (L), to produce ACSL. A novel ACSL-modified multifunctional liposomes (Lip) loaded with docetaxel (DTX; DTX-ACSL-Lip) was then prepared and characterized. DTX-ACSL-Lip recorded higher pH sensitivity and slower release than DTX-Lip and showed dithiothreitol (DTT) response release. DTX-ACSL-Lip uptake by Caco-2 cells was also significantly enhanced mainly viaA transporters compared with DTX-Lip. ACSL modification of DTX-Lip also improved oral bioavailability by 10.70-folds, with a 3.45-fold increase in C and a 1.19-fold prolongation in retention time of DTX in the blood. Moreover, the grafting degree of A significantly affected cell uptake and oral bioavailability. They also showed a significant (1.33-fold) increase in drug intratumoral distribution, as well as an increase in tumor growth inhibition rate from 54.34% to 87.51% without weight loss, compared with DTX-Lip. Therefore, modification of DTX-Lip with ACSL can significantly enhance the oral bioavailability and anti-tumor efficacy of DTX without obvious toxicity, confirming the potential of the dual strategy of targeting A transporter and controlled drug release in tumor cells in oral therapy of tumor.
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http://dx.doi.org/10.1016/j.colsurfb.2020.111499DOI Listing
February 2021

Transformable Honeycomb-Like Nanoassemblies of Carbon Dots for Regulated Multisite Delivery and Enhanced Antitumor Chemoimmunotherapy.

Angew Chem Int Ed Engl 2021 03 16;60(12):6581-6592. Epub 2021 Feb 16.

Green Catalysis Center, College of Chemistry, Zhengzhou University, Zhengzhou, 450001, China.

Tumor fibrotic stroma forms complex barriers for therapeutic nanomedicine. Although nanoparticle vehicles are promising in overcoming biological barriers for drug delivery, fibrosis causes hypoxia, immunosuppression and limited immunocytes infiltration, and thus reduces antitumor efficacy of nanosystems. Herein, we report the development of cancer-associated fibroblasts (CAFs) responsive honeycomb-like nanoassemblies of carbon dots (CDs) to spatially program the delivery of multiple therapeutics for enhanced antitumor chemoimmunotherapy. Doxorubicin (DOX) and immunotherapeutic enhancer (Fe ions) are immobilized on the surface of CDs, whereas tumor microenvironment modifier (losartan, LOS) is encapsulated within the mesopores. The drugs-loaded nanoassemblies disassociate into individual CDs to release LOS to mitigate stroma and hypoxia in response to CAFs. The individual CDs carrying DOX and Fe ion efficiently penetrate deep into tumor to trigger intensified immune responses. Our in vitro and in vivo studies show that the nanoassemblies exhibit effective T cells infiltration, tumor growth inhibition and lung metastasis prevention, thereby providing a therapeutic platform for desmoplasia solid tumor.
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http://dx.doi.org/10.1002/anie.202014397DOI Listing
March 2021

Localized fluorescent imaging of multiple proteins on individual extracellular vesicles using rolling circle amplification for cancer diagnosis.

J Extracell Vesicles 2020 Oct 11;10(1):e12025. Epub 2020 Nov 11.

Henan Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases School of Pharmaceutical Sciences Zhengzhou University Zhengzhou 450001 China.

Extracellular vesicles (EV) have attracted increasing attention as tumour biomarkers due to their unique biological property. However, conventional methods for EV analysis are mainly based on bulk measurements, which masks the EV-to-EV heterogeneity in tumour diagnosis and classification. Herein, a localized fluorescent imaging method (termed Digital Profiling of Proteins on Individual EV, DPPIE) was developed for analysis of multiple proteins on individual EV. In this assay, an anti-CD9 antibody engineered biochip was used to capture EV from clinical plasma sample. Then the captured EV was specifically recognized by multiple DNA aptamers (CD63/EpCAM/MUC1), followed by rolling circle amplification to generate localized fluorescent signals. By-analyzing the heterogeneity of individual EV, we found that the high-dimensional data collected from each individual EV would provide more precise information than bulk measurement (ELISA) and the percent of CD63/EpCAM/MUC1-triple-positive EV in breast cancer patients was significantly higher than that of healthy donors, and this method can achieve an overall accuracy of 91%. Moreover, using DPPIE, we are able to distinguish the EV between lung adenocarcinoma and lung squamous carcinoma patients. This individual EV heterogeneity analysis strategy provides a new way for digging more information on EV to achieve multi-cancer diagnosis and classification.
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http://dx.doi.org/10.1002/jev2.12025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7710127PMC
October 2020

A soft anti-virulence liposome realizing the explosive release of antibiotics at an infectious site to improve antimicrobial therapy.

J Mater Chem B 2021 01 23;9(1):147-158. Epub 2020 Nov 23.

School of Pharmaceutical Sciences, Zhengzhou University, No. 100, Kexue Avenue, Zhengzhou 450001, China.

Pore-forming toxins (PFTs), the most common virulence proteins, are promising therapeutic keys in bacterial infections. CAL02, consisting of sphingomyelin (Sm) and containing a maximum ratio of cholesterol (Ch), has been applied to sequester PFTs. However, Sm, a saturated phospholipid, leads to structural rigidity of the liposome, which does not benefit PFT combination. Therefore, in order to decrease the membrane rigidity and improve the fluidity of liposomes, we have introduced an unsaturated phospholipid, phosphatidylcholine (Pc), to the saturated Sm. In this report, a soft nanoliposome (called CSPL), composed of Ch, Sm and Pc, was artificially prepared. In order to further improve its antibacterial effect, vancomycin (Van) was loaded into the hydrophilic core of CSPL, where Van can be released radically at the infectious site through transmembrane pores formed by the PFTs in CSPL. This soft Van@CSPL nanoliposome with detoxification/drug release was able to inhibit the possibility of antibiotic resistance and could play a better role in treating severe invasive infections in mice.
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http://dx.doi.org/10.1039/d0tb02255aDOI Listing
January 2021

Dual-modal imaging-guided theranostic nanocarriers based on 2-methoxyestradiol and indocyanine green.

Int J Pharm 2021 Jan 19;592:120098. Epub 2020 Nov 19.

School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China. Electronic address:

Drug toxicity and insufficient drug dosing place a limit on the effect of chemotherapy. Optimal efficacy is achieved by exposing tumor cells to the maximum tolerated dose of a chemotherapeutic drug. In this study, we developed a strategy (graphic summary) for enhancing the therapeutic and diagnostic capabilities of known chemotherapeutics. We used a dual-mode near-infrared (NIR) fluorescence/photoacoustic imaging technology to achieve actively guided tumor targeting of the photothermal therapeutic agent indocyanine green (ICG) and the chemotherapeutic drug 2-methoxyestradiol (2-ME), which were loaded into thermosensitive liposomes (TSLs) with surface-grafted tumor-targeting peptide cRGDyk (cRGDyk-2-ME@ICG-TSLs). In vitro studies demonstrated that cRGDyk-2-ME@ICG-TSLs effectively induced drug accumulation and cytotoxicity in NIR laser-irradiated B16-F10 melanoma cells using dual targeting based on the cRGDyk peptide and temperature sensitivity. An in vivo study showed that 24 h after intravenously injecting cRGDyk-2-ME@ICG-TSLs into melanoma tumor-bearing mice, the dual-mode NIR fluorescence/photoacoustic imaging could accurately identify tumors and normal tissues. In addition, the combination of cRGDyk-2-ME@ICG-TSLs and NIR radiation suppressed tumor growth in tumor-bearing nude mice and was associated with a low risk of side effects on normal organs. Our results indicate that TSLs are a suitable drug delivery system for diagnostic and chemotherapeutic agents guided by dual-mode imaging.
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http://dx.doi.org/10.1016/j.ijpharm.2020.120098DOI Listing
January 2021

Limiting tumor cells comprehensively at micro and macro levels to improve the therapeutic effect of chemotherapy.

Nanotechnology 2021 Jan;32(1):015301

School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, People's Republic of China. Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, Zhengzhou University, Zhengzhou, Henan Province 450001, People's Republic of China.

Clinical data shows that antitumor treatments are often ineffective if tumor cells have metastasized. To gain an effective antitumor therapeutic effect, in this report, the tumor cell was limited to the primary site and simultaneously ablated by chemotherapy. Considering the extremely complicated process of cancer metastasis, we seek to comprehensively suppress tumor metastases at both micro and macro levels, which closely link to migration and interact with each other. At the micro level, the motility of the tumor cell was decreased via accelerating mitochondria fusion. At the macro level, the unfavorable hypoxia environment was improved. A liposome-based multifunctional nanomedicine was designed by coloading latrunculin B (LAT-B), an inhibitor of actin polymerization, and doxorubicin (DOX) into the hydrophobic bilayers and aqueous cavity, respectively. Meanwhile, an oxygen reservoir named perfluoropentane (PFP) was encapsulated into the liposome core to fulfill synergistic treatment of metastatic tumors. In this paper, we demonstrated that the metastasis of the tumor cell could be effectively inhibited by LAT-B through promoting mitochondria fusion without affecting its function, making it as an encouraging candidate for effective anti-metastasis therapy. Meanwhile, we found that the combination of LAT-B and DOX shows a synergistic effect against tumors because the combined effect of these two drugs cover the entire cell proliferation process. In a word, this report presents a potential improvement in the treatment of metastatic cancer.
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http://dx.doi.org/10.1088/1361-6528/abb48fDOI Listing
January 2021

Nanoenabled Intracellular Calcium Bursting for Safe and Efficient Reversal of Drug Resistance in Tumor Cells.

Nano Lett 2020 11 16;20(11):8102-8111. Epub 2020 Oct 16.

School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China.

Multidrug resistance (MDR) of a tumor is the main cause of failure of clinical chemotherapy. Herein, we report a simple, yet versatile, tumor-targeting "calcium ion nanogenerator" (TCaNG) to reverse drug resistance by inducing intracellular Ca bursting. Consequently, the TCaNG could induce Ca bursting in acidic lysosomes of tumor cells and then reverse drug resistance according to the following mechanisms: (i) Ca specifically accumulates in mitochondria, suppressing cellular respiration and relieving tumor hypoxia, thus inhibiting P-glycoprotein biosynthesis by downregulating HIF-1α expression. (ii) Ca-bursting-induced respiratory depression blocks intracellular ATP production, which further leads to the P-gp incompetence. As a result, the TCaNG could decrease the IC of DOX to MCF-7/ADR cells by approximately 30 times and reduce the proliferation of drug-resistant tumors by approximately 13 times without obvious side effects. This simple, safe, and effective "Ca bursting" strategy holds the potential for clinical application in tumor treatment.
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http://dx.doi.org/10.1021/acs.nanolett.0c03042DOI Listing
November 2020

Influence of the COVID-19 Pandemic on Quality of Life of Patients with Parkinson's Disease.

Parkinsons Dis 2020 5;2020:1216568. Epub 2020 Oct 5.

Tongren Hospital, Shanghai Jiao Tong University Medical School, Shanghai 200336, China.

Introduction: This study investigated the influence of lockdown during the 2019 coronavirus disease (COVID-19) pandemic on the quality of life of patients with Parkinson's disease (PD).

Methods: We conducted a questionnaire survey involving 113 patients with PD from Xihu District, Hangzhou, Zhejiang. During the epidemic prevention and control period (February 1 to March 31, 2020), patients enrolled were asked to fill out questionnaires, including the "COVID-19 Questionnaire for PD Patients during the Period of Epidemic Prevention and Control" and "39-item Parkinson's Disease Questionnaire (PDQ-39)." During the phase of gradual release of epidemic prevention and control (April 1 to April 30, 2020), all patients were followed up again, and PDQ-39 questionnaires were completed.

Results: The quality of life for patients during the period of epidemic prevention and control was worse than that after epidemic prevention and control ( < 0.001). The biggest problem that they faced was that they could not receive their doctor's advice or guidance regularly. The quality of life of patients who had difficulty getting doctors' guidance or those who changed their routine medication due to lockdown was even worse. Telemedicine was quite effective and efficient for patients to get doctors' guidance during lockdown.

Conclusions: The inconvenient treatment during the pandemic directly caused the aggravation of patients' symptoms and the decline in their quality of life. It is suggested that social media (such as WeChat or Tencent QQ) are used for regular interactions and follow-up appointments for patients with inconvenient medical treatment.
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http://dx.doi.org/10.1155/2020/1216568DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7537675PMC
October 2020

Co-administration of paclitaxel and 2-methoxyestradiol using folate-conjugated human serum albumin nanoparticles for improving drug resistance and antitumor efficacy.

Pharm Dev Technol 2021 Jan 6;26(1):1-10. Epub 2020 Oct 6.

School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China.

The use of chemotherapeutic drug paclitaxel (PTX) for the treatment of tumors has several limitations, including multidrug resistance (MDR) and serious adverse reactions. This research aims to co-encapsulate PTX and the chemosensitizer 2-methoxyestradiol (2-ME) into folate-conjugated human serum albumin nanoparticles (FA-HSANPs) to reduce multiple drug resistance and improve antitumor efficiency. The results show PTX/2-ME@FA-HSANPs had uniform particle size (180 ± 12.31 nm) and high encapsulation efficacy. It also exhibited highly potent cytotoxicity and apoptosis-inducing activities in the G2/M phase of PTX-resistant EC109/Taxol cells. Moreover, PTX/2-ME@FA-HSANPs not only displayed better inhibition of tumor growth in S-180 tumor-bearing mice than PTX alone but also reduced pathological damage to normal tissues. In summary, PTX/2-ME@FA-HSANPs could be a promising vehicle for tumor therapy and reducing drug resistance. This research will also provide references for other MDR treatment.
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http://dx.doi.org/10.1080/10837450.2020.1829640DOI Listing
January 2021

Modulation of Field-Effect Passivation at the Back Electrode Interface Enabling Efficient Kesterite-Type CuZnSn(S,Se) Thin-Film Solar Cells.

ACS Appl Mater Interfaces 2020 Aug 12;12(34):38163-38174. Epub 2020 Aug 12.

State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Renmin Street, Changchun 130022, P. R. China.

For further efficiency improvement in kesterite-type CuZnSn(S,Se) (CZTSSe) solar cells, it is essential to address the carrier recombination issue at the back electrode interface (BEI) caused by the undesirable built-in potential orientation toward an absorber as an -MoSe interfacial layer formed. In this regard, back surface field (BSF) incorporation, i.e., field-effect passivation, shows promise for dealing with this issue due to its positive effect in decreasing recombination at the BEI. In this study, the BSF was realized with the p-type conduction transition in interfacial layer MoSe by incorporating Nb into the back electrode. The BSF width can be tuned via modulating the carrier concentration of the absorber, which has been demonstrated by capacitance-voltage characterization. A beyond 7% efficiency BSF-applied CZTSSe solar cell is prepared, and the effects of a tunable BSF and the mechanism underpinning device performance improvement have been investigated in detail. The wider BSF distribution in the absorber induces a decrease in reverse saturation current density () due to the stronger BSF effect in suppressing BEI recombination. As a result, an accompanying increase in open-circuit voltage () and short-circuit current density () is achieved as compared to the BSF-free case. This study offers an alternative strategy to address the BEI recombination issue and also broadens the interface passivation research scope of potentially competitive kesterite solar cells.
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http://dx.doi.org/10.1021/acsami.0c10561DOI Listing
August 2020

Construction and research on size and phase 'fixed-point remodelling' intelligent drug delivery system.

J Drug Target 2021 Jan 20;29(1):108-120. Epub 2020 Aug 20.

School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China.

It is important to enhance penetration depth of nanomedicine and realise rapid drug release simultaneously at targeted tumour for improving anti-tumour efficiency of chemotherapeutic drugs. This project employed sodium alginate (Alg) as matrix material, to establish tumour-responsive nanogels with particle size conversion and drug controlled release functions. Specifically, tumour-targeting peptide CRGDK was conjugated with Alg first (CRGDK-Alg). Then, doxorubicin (DOX) was efficiently encapsulated in CRGDK-FeAlg nanogel during the cross-linking process (CRGDK-FeAlg/DOX). This system was closed during circulation. Once reaching tumour, the particle size of nanogels was reduced to ∼25 nm, which facilitated deep penetration of DOX in tumour tissues. After entering tumour cells, the size of nanogels was further reduced to ∼10 nm and DOX was released simultaneously. Meanwhile, FeAlg efficiently catalysed HO to produce •OH by Fenton reaction, achieving local chemodynamic therapy without O mediation. Results showed CRGDK-FeAlg/DOX significantly inhibited tumour proliferation with /0 of 1.13 after treatment, significantly lower than that of control group with /0 of 4.79.
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http://dx.doi.org/10.1080/1061186X.2020.1807999DOI Listing
January 2021

Detachable Nanoparticle-Enhanced Chemoimmunotherapy Based on Precise Killing of Tumor Seeds and Normalizing the Growing Soil Strategy.

Nano Lett 2020 09 6;20(9):6272-6280. Epub 2020 Aug 6.

School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou 450001, China.

Although immunogenic cell death (ICD)-based chemoimmunotherapy elicits an immune response, it always focuses on eliminating "seeds" (tumor cells) but neglects "soil" (tumor microenvironment, TME), leading to tumor growth and metastasis. Herein, a type of detachable core-shell nanoplatform (DOX@HA-MMP-2-DEAP/CXB) is developed, which could swell in the acidic TME because of the protonation of the 3-diethylaminopropyl isothiocyanate (DEAP) inner core for celecoxib (CXB) release, while hyaluronic acid@doxorubicine (HA@DOX) prodrug in the outer shell could release by the cleavage of matrix metalloproteinase-2 (MMP-2) peptide. HA@DOX targets tumor cells precisely for triggering ICD. And CXB acts on multiple immune cells to remodulate TME, such as increasing the infiltration of dendritic cells (DCs) and T cells, decreasing the infiltration of the immunosuppressive cells, and eliminating the physical barriers between T cells and tumor cells. For comparison, HA-DOCA/DOX/CXB traditional nanoparticles are constructed. And DOX@HA-MMP-2-DEAP/CXB performs an impressive antitumor effect, which shows potential in enhancing the effect of chemoimmunotherapy.
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http://dx.doi.org/10.1021/acs.nanolett.0c01415DOI Listing
September 2020

MicroRNA-responsive release of Cas9/sgRNA from DNA nanoflower for cytosolic protein delivery and enhanced genome editing.

Biomaterials 2020 10 7;256:120221. Epub 2020 Jul 7.

School of Pharmaceutical Sciences, Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, Zhengzhou University, Zhengzhou, 450001, China. Electronic address:

Nanoparticle-based CRISPR/Cas9 delivery systems hold great promise for specific and precise treatment of genetic disorder diseases. Herein, we developed a DNA nanoflower-based platform for microRNA-responsive cytosolic delivery of Cas9/sgRNA complex into tumor cells. The biocompatible DNA nano-vehicles can efficiently load Cas9/sgRNA by sequence hybridization. Importantly, this hybridization can be replaced by a tumor specific miRNA through toehold-mediated strand displacement process and achieve cell-type-specific release of Cas9/sgRNA from the DNA nanoflowers. We have verified that this miRNA-responsive releasing process can significantly improve the genome editing efficiency comparing with non-responsive control. This strategy suggests a versatile way for designing more specific and efficient CRISPR-based genome therapy system by incorporating stimuli-responsive Cas9/sgRNA release process.
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http://dx.doi.org/10.1016/j.biomaterials.2020.120221DOI Listing
October 2020

Sensitive Signal Amplifying a Diagnostic Biochip Based on a Biomimetic Periodic Nanostructure for Detecting Cancer Exosomes.

ACS Appl Mater Interfaces 2020 Jul 14;12(30):33473-33482. Epub 2020 Jul 14.

School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan Province 450001, China.

Tumor-derived exosomes are emerging noninvasive biomarker reservoirs that reflect biological information from their parental cells, especially specific markers, including proteins, DNA fragments and RNAs. Recently, analytical methods of tumor-derived exosomes have been increasing growth. However, developing a convenient signal amplification technique to improve the sensitivity of exosomes detection still remains a challenge. Herein, an ultrasensitive and specific exosomes diagnostic biochip is constructed and further applied to circulating tumor exosomes detection in serum. Using an exosomes diagnostic biochip, signal amplification is achieved by combining the advantages of quantum dots with the biomimetic periodic nanostructure of photonic crystals. Glypican-1 (GPC1), a membrane-anchored protein that is overexpressed in exosomes from pancreatic cancer, is detected using nanosized molecular beacons with high luminescence efficiency; then the signal is amplified through photonic crystals. Moreover, the method allows the quantitative analysis of various disease-specific surface proteins on exosomes. We believe that this exosomes diagnostic biochip is likely to have potential as an effective bioassay, which may be helpful for quantification of disease-specific exosomes in clinical use.
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http://dx.doi.org/10.1021/acsami.0c06785DOI Listing
July 2020

A Biomimetic Nanogenerator of Reactive Nitrogen Species Based on Battlefield Transfer Strategy for Enhanced Immunotherapy.

Small 2020 06 28;16(25):e2002138. Epub 2020 May 28.

School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, 450001, P. R. China.

Currently, cell membrane is always utilized for the construction of biomimetic nanoparticles. By contrast, mimicking the intracellular activity seems more meaningful. Inspired by the specific killing mechanism of deoxy-hemoglobin (Hb) dependent drug (RRx-001) in hypoxic red blood cells (RBC), this work aims to develop an inner and outer RBC-biomimetic antitumor nanoplatform that replicates both membrane surface properties and intracellularly certain therapeutic mechanisms of RRx-001 in hypoxic RBC. Herein, RRx-001 and Hb are introduced into RBC membrane camouflaged TiO nanoparticles. Upon arrival at hypoxic tumor microenvironment (TME), the biomimetic nanoplatform (R@HTR) is activated and triggers a series of reactions to generate reactive nitrogen species (RNS). More importantly, the potent antitumor immunity and immunomodulatory function of RNS in TME are demonstrated. Such an idea would transfer the battlefield of RRx-001 from hypoxic RBC to hypoxic TME, enhancing its combat capability. As a proof of concept, this biomimetic nanoreactor of RNS exhibits efficient tumor regression and metastasis prevention. The battlefield transfer strategy would not only present meaningful insights for immunotherapy, but also realize substantial breakthroughs in biomimetic nanotechnology.
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http://dx.doi.org/10.1002/smll.202002138DOI Listing
June 2020

Nephrological disorders and neurological involvement in pediatric primary Sjogren syndrome:a case report and review of literature.

Pediatr Rheumatol Online J 2020 May 24;18(1):39. Epub 2020 May 24.

Department of Laboratory, Tongde Hospital of Zhejiang Province, Hangzhou, People's Republic of China.

Background: Sjögren syndrome (SS) is a rare disease in pediatrics, and little attention has been paid to the clinical feature in these patients. To date, there are few cases concern about neurological and nephrological disorders in childhood Sjögren syndrome. We describe a case of Sjögren syndrome in a 12-year-old girl who developed neurological disorders and interstitial nephritis and review the literature currently available on this topic.

Case Presentation: A 12-year-old girl was admitted to our hospital for arthritis and glucosuria. She was required to do labial gland and renal biopsy, because the positive for anti-nuclear antibody and anti-Sjögren syndrome B (anti-SSB) antibody. Then the biopsy was performed revealing the lymphocytic infiltrate in the small area and renal tubular interstitial damage,thus the diagnosis of Sjögren syndrome with tubular interstitial damage was made. Three months later, she presented again with headache, fever, nausea, vomiting and was recovered without drug therapy. Based on the patient's medical history, laboratory and imaging examination, and treatment, we speculate that the disorders of the nervous system were caused by the Sjögren syndrome. The girl has stable renal function and no residual nervous system damage in the next 1.5 years, but she underwent low dose prednisone therapy because of persistent renal glucosuria.

Conclusions: Nephrological disorders and neurological involvement are rare manifestations of Sjögren syndrome in children, and rarely presented as the initial symptoms. It should be suspected in children presenting with unexplained renal diseases, neurological abnormalities, or unexplained fever. Although there is no guidelines on the diagnosis and treatment of children Sjögren syndrome are currently available, early recognition and the appropriate treatment of renal damage and neurologic involvement would improve prognosis and prevent complications.
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http://dx.doi.org/10.1186/s12969-020-00431-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7245745PMC
May 2020

Nanoenabled Disruption of Multiple Barriers in Antigen Cross-Presentation of Dendritic Cells Calcium Interference for Enhanced Chemo-Immunotherapy.

ACS Nano 2020 06 22;14(6):7639-7650. Epub 2020 May 22.

School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China.

Chemo-immunotherapy holds the advantage of specific antitumor effects by activating T cell immune response. However, the efficiency of chemo-immunotherapy is restricted to the insufficient antigen presentation of dendritic cells (DCs) in the tumor immunosuppression microenvironment. Here, we rationally designed a simple yet versatile calcium ion nanogenerator to disrupt the autophagy inhibition condition within DCs, enrich damage-associated molecular patterns (DAMPs), and attenuate acidity in the tumor microenvironment. After chemotherapy, honeycomb calcium carbonate (CaCO) nanoparticles (OVA@CaCO, denoted as HOCN, ovalbumin (OVA) acted as skeleton) could preferentially accumulate in the tumor and display a series of benefits for disrupting multiple barriers in antigen cross-presentation of DCs: (i) recovering cell viability of DCs by HOCN-induced tumor acidity attenuating; (ii) disrupting the autophagy inhibition condition in DCs by generating Ca in cells; (iii) improving maturation of DCs by Ca overloading-mediated enhanced DAMP release from tumor cells. In addition, HOCN can also disrupt the immunosuppressive microenvironment by reducing the infiltration of immunosuppressive cells and factors. We believe regulation of the intratumoral Ca offers an alternative strategy for improving cancer chemo-immunotherapy.
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http://dx.doi.org/10.1021/acsnano.0c03881DOI Listing
June 2020

Manganese-Based Nanoactivator Optimizes Cancer Immunotherapy Enhancing Innate Immunity.

ACS Nano 2020 04 20;14(4):3927-3940. Epub 2020 Apr 20.

Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, Zhengzhou University, Zhengzhou 450001, China.

Cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING) are essential components of the innate immune sensors to cytosolic DNA and elicit type I interferon (IFN). Recent studies have revealed that manganese (Mn) can enhance cGAS and STING activation to viral infection. However, the role of Mn in antitumor immunity has not been explored. Here, we designed a nanoactivator, which can induce the presence of DNA in cytoplasm and simultaneously elevate Mn accumulation within tumor cells. In detail, amorphous porous manganese phosphate (APMP) NPs that are highly responsive to tumor microenvironment were employed to construct doxorubicin (DOX)-loaded and phospholipid (PL)-coated hybrid nanoparticles (PL/APMP-DOX NPs). PL/APMP-DOX NPs were stably maintained during systemic circulation, but triggered to release DOX for inducing DNA damage and Mn to augment cGAS/STING activity. We found that PL/APMP-DOX NPs with superior tumor-targeting capacity boosted dendritic cell maturation and increased cytotoxic T lymphocyte infiltration as well as natural killer cell recruitment into the tumor site. Furthermore, the NPs increased production of type I IFN and secretion of pro-inflammatory cytokines (for example, TNF-α and IL-6). Consequently, PL/APMP-DOX NPs exhibited excellent antitumor efficacy and prolonged the lifespan of the tumor-bearing mice. Collectively, we developed a PL-decorated Mn-based hybrid nanoactivator to intensify immune activation and that might provide therapeutic potential for caner immunotherapy.
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http://dx.doi.org/10.1021/acsnano.9b06111DOI Listing
April 2020

Self-responsive co-delivery system for remodeling tumor intracellular microenvironment to promote PTEN-mediated anti-tumor therapy.

Nanoscale 2020 May 6;12(17):9392-9403. Epub 2020 Mar 6.

School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China.

Delivering the pten gene into tumor cells to reacquire PTEN functionality is considered to be an attractive method for cancer treatment. However, the inhibition effect of the tumor intracellular microenvironment (TIME), especially at the high reactive oxygen species (ROS) level, on pten expression and PTEN protein functionality was nearly overlooked. Herein, the development of a potential strategy is described, which enhances PTEN-mediated anti-tumor capability by exhausting the intracellular ROS in TIME. To achieve this, poly(ethyleneimine) (PEI)-modified DSPE was introduced to protect the pten plasmid, and form liposomes for encapsulating the "scavenger" of oxidation homeostasis, epigallocatechin-3-gallate (EGCG). Notably, this was a simple system with improved safety compared which when compared with the use of PEI could accomplish efficient pten transfection and simultaneous disintegration to cause transient release of EGCG responding to the endosome environment through the "proton sponge effect". In the cytoplasm, EGCG depleted ROS and promoted the expression of the pten gene as well as restoring protein functionality, thus negatively regulating the PI3K-AKT signaling pathway. In vitro and in vivo results revealed that this system significantly inhibited tumor growth via remodeling of the TIME, and provided a promising way to control malignant tumors.
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http://dx.doi.org/10.1039/d0nr00563kDOI Listing
May 2020

Positioning Remodeling Nanogels Mediated Codelivery of Antivascular Drug and Autophagy Inhibitor for Cooperative Tumor Therapy.

ACS Appl Mater Interfaces 2020 Feb 30;12(6):6978-6990. Epub 2020 Jan 30.

School of Pharmaceutical Sciences , Zhengzhou University , Zhengzhou 450001 , China.

Tumor vasculature and enhanced autophagy collectively provide the source of nutrients for tumor growth, invasion, and metastasis. Blocking the source of nutrients will be a novel and promising antitumor approach. Herein, we exploited an intelligent nanogel (CA4-FeAlg/HCQ) with a positioning remodeling feature to precisely kill A549 cancer cells in all directions based on frontal and rear attack strategies. CA4-FeAlg/HCQ nanogels could remain stable during blood circulation. When they reached the tumor vascular site, the vascular blocker combretastatin A4 (CA4) would be released at first to exert an antiangiogenic effect. Thereafter, FeAlg/HCQ disintegrated into small nanogels (<30 nm) for tumor deep penetration. Once small nanogels entered tumor cells, FeAlg/HCQ would undergo phase remodeling (gel to sol) to release the autophagy inhibitor hydroxychloroquine (HCQ) quickly. The autophagy induced by CA4 can be effectively inhibited by HCQ to achieve synergistic treatment of tumors. In addition, after Fe in FeAlg being reduced to Fe, it catalyzed intratumoral hydrogen peroxide (HO) to generate cytotoxic hydroxyl radicals (·OH), which further strengthened the antitumor effect. The in vivo pharmacodynamic result revealed that CA4-FeAlg/HCQ showed the greatest therapeutic effect, with the final / of 0.40 ± 0.10. Our study provided a hopeful platform for rational and precise tumor treatment, which may be of great significance in the combined pharmacotherapy.
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http://dx.doi.org/10.1021/acsami.9b22412DOI Listing
February 2020

HOTAIRM1 suppresses cell proliferation and invasion in ovarian cancer through facilitating ARHGAP24 expression by sponging miR-106a-5p.

Life Sci 2020 Feb 11;243:117296. Epub 2020 Jan 11.

Department of Gynecologic Oncology, Henan Cancer Hospital, the Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou 45003.

Aims: Ovarian cancer (OC) is the most lethal gynecologic malignant tumors all over the world. HOX antisense intergenic RNA myeloid 1 (HOTAIRM1) has been reported as an important regulator in multiple tumors. However, the functions of HOTAIRM1 in OC and its possible molecular mechanisms remain unclear.

Main Methods: qRT-PCR analysis was performed to detect the expression levels of HOTAIRM1, miR-106a-5p and ARHGAP24 mRNA in OC tissues and cells. The functional effects of HOTAIRM1, miR-106a-5p and ARHGAP24 on OC cells were determined by MTT, colony formation, flow cytometry and Transwell assays. Luciferase reporter, RIP and RNA pull-down assays were used to examine the interaction between miR-106a-5p and HOTAIRM1 or ARHGAP24. Tumor xenografts were constructed in nude mice to confirm the roles of HOTAIRM1 in OC in vivo.

Key Findings: HOTAIRM1 expression was lowered in OC tumor tissues and cells. Decreased HOTAIRM1 expression was associated with advanced FIGO stages and lymphatic metastasis. Up-regulation of HOTAIRM1 suppressed OC cell proliferation and invasion, and promoted apoptosis. Also, HOTAIRM1 slowed OC tumor growth in vivo. Moreover, HOTAIRM1 could serve as a competing endogenous RNA (ceRNA) of miR-106a-5p to derepress ARHGAP24 expression. HOTAIRM1-mediated inhibitory effect on OC progression was partly reversed following the restoration of miR-106a-5p expression. Furthermore, ARHGAP24 overexpression repressed OC progression in vitro.

Significance: In conclusion, our study showed that HOTAIRM1 suppressed OC progression through derepression of ARHGAP24 by sponging miR-106a-5p. This finding provides novel insights into the mechanisms of HOTAIRM1 in OC and highlights a potential therapeutic strategy for the treatment of OC.
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http://dx.doi.org/10.1016/j.lfs.2020.117296DOI Listing
February 2020

Single-dose in situ storage for intensifying anticancer efficacy via combinatorial strategy.

J Control Release 2020 03 8;319:438-449. Epub 2020 Jan 8.

School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China; Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, Henan Province, China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Henan Province, Zhengzhou, China. Electronic address:

Metronomic cancer chemotherapy has displayed the potential to ameliorate immunosuppressive tumor microenvironment (TME) and facilitate antitumor immunotherapy, but this strategy requires uninterrupted administration of low-dose chemotherapeutic agents and suffers from rapid drug clearance. Here, we developed a single-dose in situ immune stimulator storage to achieve prolonged retention and sustained release of drugs in tumor parenchyma. Importantly, this storage could initiate immune responses through photothermal therapy (PTT) and simultaneously remodel TME. In detail, the storage framework (NGOPC) with size of ~60 nm, was composed of Ala-Ala-Asn-Cys-Lys modified nano graphene oxide (NGO-PEG-pep) and 2-cyano-6-aminobenzothiazole modified NGO (NGO-PEG-CABT), and could sufficiently penetrate into deep tumor region. Once NGOPC arrived at the core field, legumain overexpressing in TME could trigger click cycloaddition reaction of NGO-PEG-pep with NGO-PEG-CABT to form network, leading to aggregation and augmented retention in tumor. Additionally, paclitaxel (PTX) that can block immunologic escape was loaded in NGOPC (NGOPC@PTX), which synergistically worked with PTT-generated antitumor immunity. We found that NGOPC@PTX possessed the superior ability to accumulate in tumor and generate antitumor immunological efficacy by improving immune factors: induction of HSP70-mediated immunogenic cell death, reduction of regulatory T cells, and activation of cytotoxic T lymphocyte. This in situ storage, which exhibited excellent tumor growth inhibition effect and prolonged lifespan in combination with PTT, displays the potential for intensified cancer immunotherapy.
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http://dx.doi.org/10.1016/j.jconrel.2020.01.014DOI Listing
March 2020

US-triggered ultra-sensitive "thrombus constructor" for precise tumor therapy.

J Control Release 2020 02 17;318:136-144. Epub 2019 Dec 17.

School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, PR China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Henan Province, PR China; Key laboratory of Targeting Therapy and Diagnosis for Critical Diseases, Henan Province, PR China. Electronic address:

Embolization therapy is an attractive strategy for antitumor therapy, especially for solid tumors. In vivo self-coagulation behavior holds great potential in a new type of tumor embolization therapy. However, spatiotemporal controllable in situ formation of thrombus in tumor is a challenge. Herein, an ultrasound (US)-responsive ultra-sensitive "thrombus constructor" (UUNC), which was prepared by loading thrombin into a nanobubble, and modified with NGR peptide on its surface, is rational designed for tumor embolization therapy. Benefiting from the targeting ability of NGR peptides to tumor neovascularization, UUNC efficiently enriched in tumor vessels, and then released thrombin rapidly to form thrombi in situ of tumor blood vessels in the presence of US. In vivo antitumor experiments demonstrated that UUNC could significantly lead to tumor cell apoptosis and necrosis, and the tumor growth inhibition rate (TGI) was 85.3% with a transient US in tumor, while maintain high stability, and no obvious thrombus was observed in normal tissues. UUNC holds an attractive potential for tumor embolization therapy via spatiotemporal controllable thrombus construct strategy.
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http://dx.doi.org/10.1016/j.jconrel.2019.12.029DOI Listing
February 2020