Publications by authors named "Zhifei Dai"

133 Publications

Synergies between therapeutic ultrasound, gene therapy and immunotherapy in cancer treatment.

Adv Drug Deliv Rev 2021 Jul 30:113906. Epub 2021 Jul 30.

Department of Radiology, Stanford University, Palo Alto, CA, USA. Electronic address:

Due to the ease of use and excellent safety profile, ultrasound is a promising technique for both diagnosis and site-specific therapy. Ultrasound-based techniques have been developed to enhance the pharmacokinetics and efficacy of therapeutic agents in cancer treatment. In particular, transfection with exogenous nucleic acids has the potential to stimulate an immune response in the tumor microenvironment. Ultrasound-mediated gene transfection is a growing field, and recent work has incorporated this technique into cancer immunotherapy. Compared with other gene transfection methods, ultrasound-mediated gene transfection has a unique opportunity to augment the intracellular uptake of nucleic acids while safely and stably modulating the expression of immunostimulatory cytokines. The development and commercialization of therapeutic ultrasound systems further enhance the potential translation. In this Review, we introduce the underlying mechanisms and ongoing preclinical studies of ultrasound-based techniques in gene transfection for cancer immunotherapy. Furthermore, we expand on aspects of therapeutic ultrasound that impact gene therapy and immunotherapy, including tumor debulking, enhancing cytokines and chemokines and altering nanoparticle pharmacokinetics as these effects of ultrasound cannot be fully dissected from targeted gene therapy. We finally explore the outlook for this rapidly developing field.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.addr.2021.113906DOI Listing
July 2021

SIMPLE is an endosomal regulator that protects against non-alcoholic fatty liver disease by targeting the lysosomal degradation of EGFR.

Hepatology 2021 Jul 28. Epub 2021 Jul 28.

Department of Cardiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Background & Aims: Nonalcoholic fatty liver disease (NAFLD) has become a tremendous burden for public health, however, there is no drug for NAFLD therapy at present. Impaired endo-lysosome-mediated protein degradation is observed in a variety of metabolic disorders, such as atherosclerosis, type 2 diabetes mellitus and NAFLD. Small integral membrane protein of lysosome/late endosome (SIMPLE) is a regulator of endosome-to-lysosome trafficking and cell signaling. But the role that SIMPLE plays in NAFLD progression remains unknown. Here we investigated SIMPLE function in NAFLD development and sophisticated mechanism therein.

Approach & Results: This study found in vitro knockdown of SIMPLE significantly aggravated lipid accumulation, inflammation in hepatocytes treated with metabolic stimulation. Consistently, in vivo experiments showed that liver-specific Simple-knockout (Simple-HKO) mice exhibited more severe high-fat diet (HFD)-, high-fat-high-cholesterol diet (HFHC)-, and methionine-choline-deficient diet (MCD)- induced steatosis, glucose intolerance, inflammation, and fibrosis than those fed with normal-chow diet. Meanwhile, RNA-sequencing demonstrated the up-regulated signaling pathways and signature genes involved in lipid metabolism, inflammation and fibrosis in Simple-HKO mice compared to control mice under metabolic stress. Mechanically, we found SIMPLE directly interact with epidermal growth factor receptor (EGFR). SIMPLE deficiency results in dysregulated degradation of EGFR, subsequently hyperactivated EGFR phosphorylation, exaggerating NAFLD development. Moreover, we further demonstrated that using EGFR inhibitor or silencing EGFR expression could ameliorate lipid accumulation induced by the knockdown of SIMPLE.

Conclusions: SIMPLE ameliorated NASH by prompting EGFR degradation and can also be a potential therapeutic candidate for NASH.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hep.32075DOI Listing
July 2021

Photosensitizer Nanoparticles Boost Photodynamic Therapy for Pancreatic Cancer Treatment.

Nanomicro Lett 2021 Jan 4;13(1):35. Epub 2021 Jan 4.

Department of Biomedical Engineering, College of Engineering, Peking University, No. 5 Yiheyuan Road, Haidian District, Beijing, 100871, People's Republic of China.

Patients with pancreatic cancer (PCa) have a poor prognosis apart from the few suitable for surgery. Photodynamic therapy (PDT) is a minimally invasive treatment modality whose efficacy and safety in treating unresectable localized PCa have been corroborated in clinic. Yet, it suffers from certain limitations during clinical exploitation, including insufficient photosensitizers (PSs) delivery, tumor-oxygenation dependency, and treatment escape of aggressive tumors. To overcome these obstacles, an increasing number of researchers are currently on a quest to develop photosensitizer nanoparticles (NPs) by the use of a variety of nanocarrier systems to improve cellular uptake and biodistribution of photosensitizers. Encapsulation of PSs with NPs endows them significantly higher accumulation within PCa tumors due to the increased solubility and stability in blood circulation. A number of approaches have been explored to produce NPs co-delivering multi-agents affording PDT-based synergistic therapies for improved response rates and durability of response after treatment. This review provides an overview of available data regarding the design, methodology, and oncological outcome of the innovative NPs-based PDT of PCa.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s40820-020-00561-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187547PMC
January 2021

Design and Challenges of Sonodynamic Therapy System for Cancer Theranostics: From Equipment to Sensitizers.

Adv Sci (Weinh) 2021 05 12;8(10):2002178. Epub 2021 Mar 12.

Department of Biomedical Engineering College of Engineering Peking University Beijing 100871 China.

As a novel noninvasive therapeutic modality combining low-intensity ultrasound and sonosensitizers, sonodynamic therapy (SDT) is promising for clinical translation due to its high tissue-penetrating capability to treat deeper lesions intractable by photodynamic therapy (PDT), which suffers from the major limitation of low tissue penetration depth of light. The effectiveness and feasibility of SDT are regarded to rely on not only the development of stable and flexible SDT apparatus, but also the screening of sonosensitizers with good specificity and safety. To give an outlook of the development of SDT equipment, the key technologies are discussed according to five aspects including ultrasonic dose settings, sonosensitizer screening, tumor positioning, temperature monitoring, and reactive oxygen species (ROS) detection. In addition, some state-of-the-art SDT multifunctional equipment integrating diagnosis and treatment for accurate SDT are introduced. Further, an overview of the development of sonosensitizers is provided from small molecular sensitizers to nano/microenhanced sensitizers. Several types of nanomaterial-augmented SDT are in discussion, including porphyrin-based nanomaterials, porphyrin-like nanomaterials, inorganic nanomaterials, and organic-inorganic hybrid nanomaterials with different strategies to improve SDT therapeutic efficacy. There is no doubt that the rapid development and clinical translation of sonodynamic therapy will be promoted by advanced equipment, smart nanomaterial-based sonosensitizer, and multidisciplinary collaboration.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/advs.202002178DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8132157PMC
May 2021

Tumor Necrosis Factor α-Induced Protein 8-Like 2 Alleviates Nonalcoholic Fatty Liver Disease Through Suppressing Transforming Growth Factor Beta-Activated Kinase 1 Activation.

Hepatology 2021 Sep 26;74(3):1300-1318. Epub 2021 Jul 26.

Department of Cardiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Background And Aims: NAFLD prevalence has increased rapidly and become a major global health problem. Tumor necrosis factor α-induced protein 8-like 2 (TIPE2) plays a protective role in a cluster of liver diseases, such as autoimmune hepatitis, hepatitis B, and hepatocellular carcinoma. However, the function of TIPE2 in NAFLD remains unknown. Here, we investigated the role of TIPE2 in the development of NAFLD.

Approach And Results: Our study found that in vitro overexpression or knockout of TIPE2 significantly ameliorated or aggravated lipid accumulation and inflammation in hepatocytes exposed to metabolic stimulation, respectively. Consistently, in vivo hepatic steatosis, insulin resistance, inflammation, and fibrosis were alleviated in hepatic Tipe2-transgenic mice but exaggerated in hepatic Tipe2-knockout mice treated by metabolic challenges. RNA sequencing revealed that TIPE2 was significantly associated with the mitogen-activated protein kinase pathway. Mechanistic experiments demonstrated that TIPE2 bound with transforming growth factor beta-activated kinase 1 (TAK1), prevented tumor necrosis factor receptor-associated factor 6-mediated TAK1 ubiquitination and subsequently inhibited the TAK1 phosphorylation and activation of TAK1-c-Jun N-terminal kinase (JNK)/p38 signaling. Further investigation showed that blocking the activity of TAK1 reversed the worsening of hepatic metabolic disorders and inflammation in hepatic-specific Tipe2-knockout hepatocytes and mice treated with metabolic stimulation.

Conclusions: TIPE2 suppresses NAFLD advancement by blocking TAK1-JNK/p38 pathway and is a promising target molecule for NAFLD therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hep.31832DOI Listing
September 2021

Nanotechnology assisted photo- and sonodynamic therapy for overcoming drug resistance.

Cancer Biol Med 2021 Mar 23. Epub 2021 Mar 23.

Institute of Translational Medicine, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen 518039, China.

Drug resistance is considered the most important reason for the clinical failure of cancer chemotherapy. Circumventing drug resistance and improving the efficacy of anticancer agents remains a major challenge. Over the past several decades, photodynamic therapy (PDT) and sonodynamic therapy (SDT) have attracted substantial attention for their efficacy in cancer treatment, and have been combined with chemotherapy to overcome drug resistance. However, simultaneously delivering sensitizers and chemotherapy drugs to same tumor cell remains challenging, thus greatly limiting this combinational therapy. The rapid development of nanotechnology provides a new approach to solve this problem. Nano-based drug delivery systems can not only improve the targeted delivery of agents but also co-deliver multiple drug components in single nanoparticles to achieve optimal synergistic effects. In this review, we briefly summarize the mechanisms of drug resistance, discuss the advantages and disadvantages of PDT and SDT in reversing drug resistance, and describe state-of-the-art research using nano-mediated PDT and SDT to solve these refractory problems. This review also highlights the clinical translational potential for this combinational therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.20892/j.issn.2095-3941.2020.0328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8185853PMC
March 2021

Key considerations in designing CRISPR/Cas9-carrying nanoparticles for therapeutic genome editing.

Nanoscale 2020 Oct;12(41):21001-21014

Department of Biomedical Engineering, College of Engineering, Peking University, Beijing 100871, China.

CRISPR-Cas9, the breakthrough genome-editing technology, has emerged as a promising tool to prevent and cure various diseases. The efficient genome editing technology strongly relies on the specific and effective delivery of CRISPR/Cas9 cargos. However, the lack of a safe, specific, and efficient non-viral delivery system for in vivo genome editing remains a major limit for its clinical translation. In this review, we will first briefly introduce the working mechanism of CRISPR/Cas9 and the patterns of CRISPR/Cas9 delivery. Furthermore, the physiological obstacles for the delivery process in vivo are elaborated. Finally, the key considerations will be deeply discussed in designing non-viral nanovectors for therapeutic CRISPR/Cas9 delivery in vivo, including the effective encapsulation of large-size macromolecules, targeting specific tissues and cells, efficient endosomal escape and safety concerns of the vector systems, in the hope of inviting more comprehensive studies on the development of safe, specific, and efficient non-viral nanovectors for delivering a CRISPR/Cas9 system.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d0nr05452fDOI Listing
October 2020

Cyanine conjugates in cancer theranostics.

Bioact Mater 2021 Mar 29;6(3):794-809. Epub 2020 Sep 29.

Department of Biomedical Engineering, College of Engineering, Peking University, Beijing 100871, China.

Cyanine is a meritorious fluorogenic core for the construction of fluorescent probes and its phototherapeutic potential has been enthusiastically explored as well. Alternatively, the covalent conjugation of cyanine with other potent therapeutic agents not only boosts its therapeutic efficacy but also broadens its therapeutic modality. Herein, we summarize miscellaneous cyanine-therapeutic agent conjugates in cancer theranostics from literature published between 2014 and 2020. The application scenarios of such theranostic cyanine conjugates covered common cancer therapeutic modalities, including chemotherapy, phototherapy and targeted therapy. Besides, cyanine conjugates that serve as nanocarriers for drug delivery are introduced as well. In an additional section, we analyze the potential of these conjugates for clinical translation. Overall, this review is aimed to stimulate research interest in exploring unattempted therapeutic agents and novel conjugation strategies and hopefully, accelerate clinical translation in this field.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bioactmat.2020.09.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7528000PMC
March 2021

Cyanine Conjugate-Based Biomedical Imaging Probes.

Adv Healthc Mater 2020 11 1;9(22):e2001327. Epub 2020 Oct 1.

Department of Biomedical Engineering, College of Engineering, Peking University, Beijing, 100871, China.

Cyanine is a class of fluorescent dye with meritorious fluorescence properties and has motivated numerous researchers to explore its imaging capabilities by miscellaneous structural modification and functionalization strategies. The covalent conjugation with other functional molecules represents a distinctive design strategy and has shown immense potential in both basic and clinical research. This review article summarizes recent achievements in cyanine conjugate-based probes for biomedical imaging. Particular attention is paid to the conjugation with targeting warheads and other contrast agents for targeted fluorescence imaging and multimodal imaging, respectively. Additionally, their clinical potential in cancer diagnostics is highlighted and some concurrent impediments for clinical translation are discussed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/adhm.202001327DOI Listing
November 2020

[email protected] Nanoparticles for Tumor Hypoxia Relief to Enhance Photodynamic Therapy against Liver Metastasis of Colon Cancer.

ACS Nano 2020 10 16;14(10):13569-13583. Epub 2020 Sep 16.

Department of Biomedical Engineering, College of Engineering, Peking University, Beijing 100871, China.

Photodynamic therapy (PDT) shows great promise for the treatment of colon cancer. However, practically, it is a great challenge to use a nanocarrier for the codelivery of both the photosensitizer and oxygen to improve PDT against PDT-induced hypoxia, which is closely related to tumor metastasis. Hence, an effective strategy was proposed to develop an oxygen self-supplemented PDT nanocarrier based on the ultrasonic dispersion of perfluorooctyl bromide (PFOB) liquid into the preformed porphyrin grafted lipid (PGL) nanoparticles (NPs) with high porphyrin loading content of 38.5%, followed by entrapping oxygen. Interestingly, the orderly arranging mode of porphyrins and alkyl chains in PGL NPs not only guarantees a high efficacy of singlet oxygen generation but also reduces fluorescence loss of porphyrins to enable PGL NPs to be highly fluorescent. More importantly, PFOB liquid was stabilized inside PGL NPs with an ultrahigh loading content of 98.15% due to the strong hydrophobic interaction between PGL and PFOB molecules, facilitating efficient oxygen delivery. Both and results demonstrated that the obtained [email protected]@PGL NPs could act as a prominent oxygen reservoir and effectively replenish oxygen into the hypoxic tumors with no need for external stimulation, conducive to augmented singlet oxygen generation, hypoxia relief, and subsequent downregulation of COX-2 expression. As a result, the use of [email protected]@PGL NPs for hypoxia relief dramatically inhibits tumor growth and liver metastasis in an HT-29 colon cancer mouse model. In addition, the [email protected]@PGL NPs could serve as a bimodal contrast agent to enhance fluorescence and CT imaging, visualizing nanoparticle accumulation to guide the subsequent laser irradiation for precise PDT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsnano.0c05617DOI Listing
October 2020

Fibronectin-targeted dual-acting micelles for combination therapy of metastatic breast cancer.

Signal Transduct Target Ther 2020 02 7;5(1):12. Epub 2020 Feb 7.

Department of Biomedical Engineering, College of Engineering, Peking University, Beijing, 100871, China.

Stage IV breast cancer, which has a high risk of invasion, often develops into metastases in distant organs, especially in the lung, and this could threaten the lives of women. Thus, the development of more advanced therapeutics that can efficiently target metastatic foci is crucial. In this study, we built an dual-acting therapeutic strategy using micelles with high stability functionalized with fibronectin-targeting CREKA peptides encapsulating two slightly soluble chemotherapy agents in water, doxorubicin (D) and vinorelbine (V), which we termed C-DVM. We found that small C-DVM micelles could efficiently codeliver drugs into 4T1 cells and disrupt microtubule structures. C-DVM also exhibited a powerful ability to eradicate and inhibit invasion of 4T1 cells. Moreover, an in vivo pharmacokinetics study showed that C-DVM increased the drug circulation half-life and led to increased enrichment of drugs in lung metastatic foci after 24 h. Moreover, dual-acting C-DVM treatment led to 90% inhibition of metastatic foci development and reduced invasion of metastases. C-DVM could potentially be used as a targeted treatment for metastasis and represents a new approach with higher therapeutic efficacy than conventional chemotherapy for stage IV breast cancer that could be used in the future.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41392-019-0104-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7005157PMC
February 2020

Glutathione-responsive disassembly of disulfide dicyanine for tumor imaging with reduction in background signal intensity.

Theranostics 2020 12;10(5):2130-2140. Epub 2020 Jan 12.

Department of Biomedical Engineering, College of Engineering, Peking University, Beijing 100871, China.

Near-infrared (NIR) fluorescence imaging has been proved as an effective modality in identifying the tumor border and distinguishing the tumor cells from healthy tissue during the oncological surgery. Developing NIR fluorescent probes with high tumor to background (T/B) signal is essential for the complete debulking of the tumor, which will prolong the survival rate of tumor patients. However, the nonspecific binding and "always-on" properties of the conventional fluorescent probes leads to high background signals and poor specificity. : To address this problem, glutathione (GSH)-responsive, two disulfide-bonded dicyanine dyes ( and ) were synthesized. As synthesized dyes are quenched under normal physiological conditions, however, once reached to the tumor site, these dyes are capable of emitting strong fluorescence signals primarily because of the cleavage of the disulfide bond in the tumor microenvironment with high GSH concentration. Besides, the GSH-responsive behavior of these dyes was monitored using the UV-vis and fluorescence spectroscopy. The diagnostic accuracy of the aforementioned dyes was also tested both in tumor cells and 4T1-bearing mice. : The fluorescence signal intensity of disulfide dicyanine dyes was quenched up to 89% compared to the mono cyanine dyes, thus providing a very low fluorescence background. However, when the disulfide dicyanine dye reaches the tumor site, the dicyanine is cleaved by GSH into two mono-dyes with high fluorescence strength, thus producing strong fluorescent signals upon excitation. The fluorescent signal of the dicyanine was enhanced by up to 27-fold after interacting with the GSH solution. xenografts tumor studies further revealed that the fluorescence signals of aforementioned dyes can be quickly recovered in the solid tumor. : In summary, the disulfide dicyanines dyes can provide a promising platform for specific tumor-activatable fluorescence imaging with improved T/B value.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7150/thno.39673DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7019170PMC
April 2021

Molecular Imaging.

Bioconjug Chem 2020 02;31(2):157-158

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.bioconjchem.0c00044DOI Listing
February 2020

Ultrasound/Optical Dual-Modality Imaging for Evaluation of Vulnerable Atherosclerotic Plaques with Osteopontin Targeted Nanoparticles.

Macromol Biosci 2020 02 29;20(2):e1900279. Epub 2019 Dec 29.

Medical School of Chinese PLA and National Clinical Research Center of Geriatric Disease, Second Medical Center, Chinese PLA General Hospital, Beijing, 100853, China.

Because of the high mortality of coronary atherosclerotic heart diseases, it is necessary to develop novel early detection methods for vulnerable atherosclerotic plaques. Phenotype transformation of vascular smooth muscle cells (VSMCs) plays a vital role in progressed atherosclerotic plaques. Osteopontin (OPN) is one of the biomarkers for phenotypic conversion of VSMCs. Significant higher OPN expression is found in foam cells along with the aggravating capacity of macrophage recruitment due to its arginine-glycine-aspartate sequence and interaction with CD44. Herein, a dual-modality imaging probe, OPN targeted nanoparticles (Cy5.5-anti-OPN-PEG-PLA-PFOB, denoted as COP-NPs), is constructed to identify the molecular characteristics of high-risk atherosclerosis by ultrasound and optical imaging. Characterization, biocompatibility, good binding sensibility, and specificity are evaluated in vitro. For in vivo study, apolipoprotein E deficien (ApoE ) mice fed with high fat diet for 20-24 weeks are used as atherosclerotic model. Ultrasound and optical imaging reveal that the nanoparticles are accumulated in the vulnerable atherosclerotic plaques. OPN targeted nanoparticles are demonstrated to be a good contrast agent in molecular imaging of synthetic VSMCs and foam cells, which can be a promising tool to identify the vulnerable atherosclerotic plaques.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/mabi.201900279DOI Listing
February 2020

Enhancing cancer therapeutic efficacy through ultrasound-mediated micro-to-nano conversion.

Wiley Interdiscip Rev Nanomed Nanobiotechnol 2020 05 12;12(3):e1604. Epub 2019 Dec 12.

Department of Biomedical Engineering, College of Engineering, Peking University, Beijing, China.

Over the last century, significant progress has been made towards the development of microbubbles (MBs) as a contrast agent for imaging and as a carrier for the delivery of therapeutic moieties. The unparalleled ability of MBs to respond to ultrasound (US) render them advantageous for molecular imaging, and US-responsive targeted delivery. However, the use of MBs has broadened far beyond the imaging contrast agent or drug delivery system alone. Notably, there has been an enormous surge in the design and fabrication of multimodal MBs for cancer therapy. Furthermore, MBs in the presence of the US has unique ability to convert itself from the micro to nanoscale, which offers diagnostic and therapeutic ability in both dimensions. In this review, we summarize the design considerations of MBs, with particular emphasize on their size and composition. In addition, different MBs formulations are discussed in the context of their current progress as an imaging contrast agent and a vehicle for drug/gene delivery. We further highlight recent advancements in the micro-to-nano conversion of MBs and their potential application for cancer theranostics. This article is characterized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Therapeutic Approaches and Drug Discovery > Emerging Technologies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/wnan.1604DOI Listing
May 2020

Manganese(iii)-chelated porphyrin microbubbles for enhanced ultrasound/MR bimodal tumor imaging through ultrasound-mediated micro-to-nano conversion.

Nanoscale 2019 May;11(21):10178-10182

Department of Biomedical Engineering, College of Engineering, Peking University, Beijing 100871, People's Republic of China.

Manganese(iii)-chelated porphyrin microbubbles (MnP-MBs) were fabricated by self-assembly from a Mn-chelated porphyrin lipid followed by encapsulating perfluoropropane-an inert gas. The obtained MnP-MBs exhibited enhanced ultrasound imaging ability after intravenous injection. Under the guidance of ultrasound imaging, MnP-MBs could be converted into nanoparticles in situ with local tumor ultrasound disruption, achieving rapid tumor MRI contrast enhancement within 30 min at a very low Mn injection dose of 0.09 mg (1.65 μmol) per kg.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/c9nr01373cDOI Listing
May 2019

Bioluminescence Imaging of Inflammation in Vivo Based on Bioluminescence and Fluorescence Resonance Energy Transfer Using Nanobubble Ultrasound Contrast Agent.

ACS Nano 2019 05 8;13(5):5124-5132. Epub 2019 May 8.

Department of Biomedical Engineering College of Engineering , Peking University , Beijing 100871 , China.

Inflammation is an immunological response involved in various inflammatory disorders ranging from neurodegenerative diseases to cancers. Luminol has been reported to detect myeloperoxidase (MPO) activity in an inflamed area through a light-emitting reaction. However, this method is limited by low tissue penetration and poor spatial resolution. Here, we fabricated a nanobubble (NB) doped with two tandem lipophilic dyes, red-shifting luminol-emitted blue light to near-infrared region through a process integrating bioluminescence resonance energy transfer (BRET) and fluorescence resonance energy transfer (FRET). This BRET-FRET process caused a 24-fold increase in detectable luminescence emission over luminol alone in an inflammation model induced by lipopolysaccharide. In addition, the echogenicity of the BRET-FRET NBs also enables perfused tissue microvasculature to be delineated by contrast-enhanced ultrasound imaging with high spatial resolution. Compared with commercially available ultrasound contrast agent, the BRET-FRET NBs exhibited comparable contrast-enhancing capability but much smaller size and higher concentration. This bioluminescence/ultrasound dual-modal contrast agent was then successfully applied for imaging of an animal model of breast cancer. Furthermore, biosafety experiments revealed that multi-injection of luminol and NBs did not induce any observable abnormality. By integrating the advantages of bioluminescence imaging and ultrasound imaging, this BRET-FRET system may have the potential to address a critical need of inflammation imaging.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsnano.8b08359DOI Listing
May 2019

Solution growth of 1D zinc tungstate (ZnWO) nanowires; design, morphology, and electrochemical sensor fabrication for selective detection of chloramphenicol.

J Hazard Mater 2019 04 20;367:205-214. Epub 2018 Dec 20.

Nanobiotech Group, National Institute for Biotechnology and Genetic Engineering (NIBGE), P.O. Box. 577, Jhang Road, Faisalabad, 38000, Pakistan; Nanobiomaterials Group, Ningbo Institute of Materials Technology and Engineering (NIMTE), Chinese Academy of Sciences, Ningbo City, Zhejiang, China. Electronic address:

Development of 1D nanostructures with novel morphology is a recent scientific attraction, so to say yielding unusual materials for advanced applications. In this work, we have prepared solution grown, single-pot 1D ZnWO nanowires (NWs) and the morphology is assessed for label-free but selective detection of chloramphenicol. This is the first report where, such structures are being investigated for this purpose. Transmission electron microscopy shows the presence of strands of ZnWO of about 20 nm in diameter. The formed NWs were highly dispersed in nature with uniform size and shape. X-ray diffraction analysis confirmed high purity of the designed NWs despite solution synthesis. X-ray photoelectron spectroscopy confirmed surface valence state of ZnWO. Fourier transform infrared spectroscopy was employed for the ascription of functional groups, whereas, optical properties were investigated using photoluminescence. NWs were employed for the detection of a model antibiotic, chloramphenicol. The developed sensor exhibited excellent limit of detection, 0.32 μM and 100% specificity as compared to its structural and functional analogues such as thiamphenicol and clindamycin. This work can broaden new opportunities for the researchers to explore unconventional nanomaterials bearing unique morphologies and quantum phenomenon for the label-free detection of other bioanalytes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jhazmat.2018.12.072DOI Listing
April 2019

Doxorubicin and indocyanine green loaded superparamagnetic iron oxide nanoparticles with PEGylated phospholipid coating for magnetic resonance with fluorescence imaging and chemotherapy of glioma.

Int J Nanomedicine 2019 20;14:101-117. Epub 2018 Dec 20.

Department of Biomedical Engineering, College of Engineering, Peking University, Beijing, China,

Background: Glioma represents the most common malignant brain tumor. Outcomes of surgical resection are often unsatisfactory due to low sensitivity or resolution of imaging methods. Moreover, the use of traditional chemotherapeutics, such as doxorubicin (DOX), is limited due to their low blood-brain barrier (BBB) permeability. Recently, the development of nanotechnology could overcome these obstacles.

Materials And Methods: Hydrophobic superparamagnetic iron oxide nanoparticles (SPIO NPs) were prepared with the use of thermal decomposition method. They were coated with 1,2-distearoyl-sn-glycero-3-phosphoethanolamine--[methoxy(polyethylene glycol)-2000] (DSPE-PEG 2000) and DOX using a thin-film hydration method followed by loading of indocyanine green (ICG) into the phospholipid layers. Details regarding the characteristics of NPs were determined. The in vitro biocompatibility and antitumor efficacy were established with the use of MTT assay. In vivo fluorescence and magnetic resonance (MR) imaging were used to evaluate BBB penetration and accumulation of NPs at the tumor site. Antitumor efficacy was evaluated using measures of tumor size, median survival times, body weights, and H&E staining.

Results: The multifunctional NPs generated had an average diameter of 22.9 nm, a zeta potential of -38.19 mV, and were capable of providing a sustained release of DOX. In vitro experiments demonstrated that the [email protected]/DOX/ICG NPs effectively enhanced cellular uptake of DOX as compared with that of free DOX. In vivo fluorescence and MR imaging revealed that the NPs not only effectively crossed the BBB but selectively accumulated at the tumor site. Meanwhile, among all groups studied, C6 glioma-bearing rats treated with the NPs exhibited the maximal degree of therapeutic efficacy, including smallest tumor volume, lowest body weight loss, and longest survival times, with no obvious side effects.

Conclusion: These results suggest that the [email protected]/DOX/ICG NPs can not only function as a nanoprobe for MR and fluorescence bimodal imaging, but also as a vehicle to deliver chemotherapeutic drugs to the tumor site, to achieve the theranostic treatment of glioma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/IJN.S173954DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6304244PMC
February 2019

Self-assembly of porphyrin-grafted lipid into nanoparticles encapsulating doxorubicin for synergistic chemo-photodynamic therapy and fluorescence imaging.

Theranostics 2018 3;8(19):5501-5518. Epub 2018 Nov 3.

Department of Biomedical Engineering, College of Engineering, Peking University, Beijing 100871, China.

The limited clinical efficacy of monotherapies in the clinic has urged the development of novel combination platforms. Taking advantage of light-triggered photodynamic treatment combined together with the controlled release of nanomedicine, it has been possible to treat cancer without eliciting any adverse effects. However, the challenges imposed by limited drug loading capacity and complex synthesis process of organic nanoparticles (NPs) have seriously impeded advances in chemo-photodynamic combination therapy. In this experiment, we utilize our previously synthesized porphyrin-grafted lipid (PGL) NPs to load highly effective chemotherapeutic drug, doxorubicin (DOX) for synergistic chemo-photodynamic therapy. A relatively simple and inexpensive rapid injection method was used to prepare porphyrin-grafted lipid (PGL) NPs. The self-assembled PGL NPs were used further to encapsulate DOX a pH-gradient loading protocol. The self-assembled liposome-like PGL NPs having a hydrophilic core were optimized to load DOX at an encapsulation efficiency (EE) of ~99%. The resultant PGL-DOX NPs were intact, highly stable and importantly these NPs successfully escaped from the endo-lysosomal compartment after laser irradiation to release DOX in the cytosol. The therapeutic efficacy of the aforementioned formulation was validated both and . PGL-DOX NPs demonstrated excellent cellular uptake, chemo-photodynamic response, and fluorescence imaging ability in different cell lines. Under laser irradiation, cells treated with a low molar concentration of PGL-DOX NPs reduced cell viability significantly. Moreover, experiments conducted in a xenograft mouse model further demonstrated the excellent tumor accumulation capability of PGL-DOX NPs driven by the enhanced permeability and retention (EPR) effect. Through fluorescence imaging, the biodistribution of PGL-DOX NPs in tumor and major organs was also easily monitored in real time . The inherent ability of porphyrin to generate ROS under laser irradiation combined with the cytotoxic effect of the anticancer drug DOX significantly suppressed tumor growth . : In summary, the PGL-DOX NPs combined chemo-photodynamic nanoplatform may serve as a potential candidate for cancer theranostics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7150/thno.27721DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6276084PMC
September 2019

Fluorescence Guided Sentinel Lymph Node Mapping: From Current Molecular Probes to Future Multimodal Nanoprobes.

Bioconjug Chem 2019 01 17;30(1):13-28. Epub 2018 Dec 17.

Department of Biomedical Engineering, College of Engineering , Peking University , Beijing 100871 , China.

For SLN lymph node biopsy (SLNB), SLN mapping has become a standard of care procedure that can accurately locate the micrometastases disseminated from primary tumor sites to the regional lymph nodes. The broad array of SLN mapping has prompted the development of a wide range of SLN tracers, rationally designed for noninvasive and high-resolution imaging of SLNs. At present, conventional SLN imaging probes (blue dyes, radiocolloids, and few other small-molecular dyes), although serving the clinical needs, are often associated with major issues such as insufficient accumulation in SLN, short retention time, staining of the surgical field, and other adverse side effects. In a recent advancement, newly designed fluorescent nanoprobes are equipped with novel features that could be of high interest in SLN mapping such as (i) a unique niche that is not met by any other conventional SLN probes, (ii) their adoptable synthesis method, and (ii) excellent sensitivity facilitating high resolution SLN mapping. Most importantly, lots of effort has been devoted for translating the fluorescent nanoprobes into a clinical setup and also imparting the multimodal imaging abilities of nanoprobes for the excellent diagnosis of life-threatening diseases such as cancer. In this review, we will provide a detailed roadmap of the progress of a wide variety of current fluorescent molecular probes and emphasize the future of nanomaterial-based single/multimodal imaging probes that have true potential translation abilities for SLN mapping.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.bioconjchem.8b00812DOI Listing
January 2019

Amphiphilic Drug Conjugates as Nanomedicines for Combined Cancer Therapy.

Bioconjug Chem 2018 12 28;29(12):3967-3981. Epub 2018 Nov 28.

Department of Biomedical Engineering, College of Engineering , Peking University , Beijing , 100871 , China.

Chemotherapy suffers from some limitations such as poor bioavailability, rapid clearance from blood, poor cellular uptake, low tumor accumulation, severe side effects on healthy tissues and most importantly multidrug resistance (MDR) in cancer cells. Nowadays, a series of smart drug delivery system (DDS) based on amphiphilic drug conjugates (ADCs) has been developed to solve these issues, including polymer-drug conjugate (PDC), phospholipid-mimicking prodrugs, peptide-drug conjugates (PepDCs), pure nanodrug (PND), amphiphilic drug-drug conjugate (ADDC), and Janus drug-drug conjugate (JDDC). These ADCs can self-assemble into nanoparticles (NPs) or microbubbles (MBs) for targeted drug delivery by minimizing the net amount of excipients, realizing great goals, such as stealth behavior and physical integrity, high drug loading content, no premature leakage, long blood circulation time, fixed drug combination, and controlled drug-release kinetics. Besides, these self-assembled systems can be further used to load additional therapeutic agents and imaging contrast agents for combined therapy, personalized monitoring of in vivo tumor targeting, and the pharmacokinetics of drugs for predicting the therapeutic outcome. In this review, we will summarize the latest progress in the development of ADCs based combination chemotherapy and discuss the important roles for overcoming the tumor MDR.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.bioconjchem.8b00692DOI Listing
December 2018

Multicolor nanobubbles for FRET/ultrasound dual-modal contrast imaging.

Nanoscale 2018 Nov;10(43):20347-20353

Department of Biomedical Engineering, College of Engineering, Peking University, Beijing 100871, China.

The aim of this paper is to develop a novel fluorescence/ultrasound dual-modal contrast agent. We prepared multicolor nanobubbles by doping with three fluorescent dyes for combined fluorescence and contrast enhanced ultrasound imaging. The nanobubbles based on fluorescence resonance energy transfer (FRET) with different doping dye ratio combinations exhibited multiple colors under single wavelength excitation, allowing multiplexed assays for various biomedical applications. In vitro and in vivo ultrasound imaging indicated that nanobubbles have great contrast enhancement capability. In vivo fluorescence imaging showed the excellent ability to provide simultaneous multicolor imaging. The novel multicolor nanobubbles may have great potential for a variety of applications in the study of life science and clinical medicine.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/c8nr05488fDOI Listing
November 2018

Photothermal therapy and photoacoustic imaging via nanotheranostics in fighting cancer.

Chem Soc Rev 2019 Apr;48(7):2053-2108

Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD 20892, USA.

The nonradiative conversion of light energy into heat (photothermal therapy, PTT) or sound energy (photoacoustic imaging, PAI) has been intensively investigated for the treatment and diagnosis of cancer, respectively. By taking advantage of nanocarriers, both imaging and therapeutic functions together with enhanced tumour accumulation have been thoroughly studied to improve the pre-clinical efficiency of PAI and PTT. In this review, we first summarize the development of inorganic and organic nano photothermal transduction agents (PTAs) and strategies for improving the PTT outcomes, including applying appropriate laser dosage, guiding the treatment via imaging techniques, developing PTAs with absorption in the second NIR window, increasing photothermal conversion efficiency (PCE), and also increasing the accumulation of PTAs in tumours. Second, we introduce the advantages of combining PTT with other therapies in cancer treatment. Third, the emerging applications of PAI in cancer-related research are exemplified. Finally, the perspectives and challenges of PTT and PAI for combating cancer, especially regarding their clinical translation, are discussed. We believe that PTT and PAI having noteworthy features would become promising next-generation non-invasive cancer theranostic techniques and improve our ability to combat cancers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/c8cs00618kDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6437026PMC
April 2019

Polarization-based super-resolution imaging of surface-enhanced Raman scattering nanoparticles with orientational information.

Nanoscale 2018 Nov;10(42):19757-19765

Department of Biomedical Engineering, College of Engineering, Peking University, Beijing 100871, China.

Raman scattering provides key information of the biological environment through light-molecule interaction; yet, it is generally very weak to detect. Surface-enhanced Raman scattering (SERS) can boost the Raman signal by several orders-of-magnitude, and thus is highly attractive for biochemical sensing. However, conventional super-resolution imaging of SERS is challenging as the Raman signal is generated from the virtual state which cannot be easily modulated as fluorescence. Here, we demonstrate super-resolution microscopy with a surface-enhanced Raman scattering (SERS) signal, with a resolution of approximately 50 nm. By modulating the polarization angle of the excitation laser, the SERS nanorods display a dramatic anisotropy effect, allowing nanoscale orientation determination of multiple dipoles with dense concentration. Furthermore, a well-established defocused analysis was performed to reconfirm the orientation accuracy of super-resolved SERS nanorods. Sub-diffraction resolution was achieved in the imaging of SERS nanorod labeled vesicles in fixed macrophages. Finally, we demonstrate dynamic SERS nanorod tracking in living macrophages, which provides not only the particle trajectory with high spatial resolution but also the rotational changes at the nanometer scale. This pioneering study paves a new way for subcellular super-resolution imaging with the SERS effect, shedding light on wider biological applications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/c8nr04808hDOI Listing
November 2018

Loading Lovastatin into Camptothecin-Floxuridine Conjugate Nanocapsules for Enhancing Anti-metastatic Efficacy of Cocktail Chemotherapy on Triple-negative Breast Cancer.

ACS Appl Mater Interfaces 2018 Sep 23;10(35):29385-29397. Epub 2018 Aug 23.

Department of Biomedical Engineering, College of Engineering , Peking University , Beijing 100871 , China.

Triple-negative breast cancer (TNBC) is a malignant and refractory disease with high morbidity and mortality. The TNBC shows no response to hormonal therapy nor targeted therapy due to the lack of known targetable biomarkers. Furthermore, the TNBC also exhibits a high degree of heterogeneity that leads to cancer evolution, drug resistance, metastatic progression, and recurrence, arising from the tumor-initiating properties of cancer stem cells (CSCs). Thus, the development of radical therapeutic regimens with high efficacy and limited side effects is crucial. In this study, we designed an innovative ternary cocktail chemotherapy by using Lovastatin (L)-loaded Janus camptothecin-floxuridine conjugate (CF) nanocapsules (NCs) with ultrahigh drug loading capacity. The obtained LCF NCs were shown to be able to suppress growth of TNBC, including inhibition of growth and metastasis of CSCs, both in vitro and in tumor-bearing mice. Moreover, in animal experiments, the LCF NCs showed sustained and synchronous drug release (half-life > 300 min), 85.2% reduction in pulmonary metastases, and no cancer recurrence during one-month observation post-treatment. Thus, this innovative LCF NC design provides a simple and synergistic strategy for the development of simultaneous triple chemotherapy and could be an efficacious, safe, and amenable choice with higher therapeutic relevance and fewer toxic complications than conventional multidrug delivery systems for TNBC treatment in the future.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsami.8b11723DOI Listing
September 2018

Ultrasound Triggered Conversion of Porphyrin/Camptothecin-Fluoroxyuridine Triad Microbubbles into Nanoparticles Overcomes Multidrug Resistance in Colorectal Cancer.

ACS Nano 2018 07 18;12(7):7312-7326. Epub 2018 Jun 18.

Department of Biomedical Engineering, College of Engineering , Peking University , Beijing 100871 , People's Republic of China.

Multidrug resistance remains one of the main obstacles to efficient chemotherapy of colorectal cancer. Herein, an efficient combination therapeutic strategy is proposed based on porphyrin/camptothecin-floxuridine triad microbubbles (PCF-MBs) with high drug loading contents, which own highly stable co-delivery drug combinations and no premature release. The triad PCF-MBs can act not only as a contrast agent for ultrasound (US)/fluorescence bimodal imaging but also a multimodal therapeutic agent for synergistic chemo-photodynamic combination therapy. Upon local ultrasound exposure under the guidance of ultrasound imaging, in situ conversion of PCF-MBs into porphyrin/camptothecin-floxuridine nanoparticles (PCF-NPs) leads to high accumulation of chemo-drugs and photosensitizer in tumors due to the induced high permeability of the capillary wall and cell membrane temporarily via sonoporation effect, greatly reducing the risk of systemic exposure. Most importantly, it was found that the PCF-MB-mediated photodynamic therapy could significantly reduce the expression of adenosine-triphosphate (ATP)-binding cassette subfamily G member 2 (ABCG), which is responsible for the drug resistance in chemotherapy, resulting in a prominent intracellular camptothecin increase. In vivo experiments revealed that the PCF-MBs in combination with ultrasound and laser irradiation could achieve a 90% tumor inhibition rate of HT-29 cancer with no recurrence. Therefore, such triad PCF-MB-based combination therapeutic strategy shows great promise for overcoming drug resistance of colorectal cancer and other cancers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsnano.8b03674DOI Listing
July 2018

Cerasomes and Bicelles: Hybrid Bilayered Nanostructures With Silica-Like Surface in Cancer Theranostics.

Front Chem 2018 18;6:127. Epub 2018 Apr 18.

Department of Biomedical Engineering, College of Engineering, Peking University, Beijing, China.

Over years, theranostic nanoplatforms have provided a new avenue for the diagnosis and treatment of various cancer types. To this end, a myriad of nanocarriers such as polymeric micelles, liposomes, and inorganic nanoparticles (NPs) with distinct physiochemical and biological properties are routinely investigated for preclinical and clinical studies. So far, liposomes have received great attention for various biomedical applications, however, it still suffers from insufficient morphological stability. On the other hand, inorganic NPs depicting excellent therapeutic ability have failed to address biocompatibility issues. This has raised a serious concern about the clinical approval of multifunctional organic or inorganic-based theranostic agents. Recently, partially silica coated nanohybrids such as cerasomes and bicelles demonstrating both diagnostic and therapeutic ability in a single system, have drawn profound attention as a fascinating novel drug delivery system. Compared with traditional liposomal or inorganic-based nanoformulations, this new and highly stable nanocarriers integrates the functional attributes of biomimetic liposomes and silica NPs, therefore, synergize strengths and functions, or even surpass weaknesses of individual components. This review at its best enlightens the emerging concept of such partially silica coated nanohybrids, fabrication strategies, and theranostic opportunities to combat cancer and related diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fchem.2018.00127DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5915561PMC
April 2018
-->