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| 1 | An enzyme-responsive and transformable PD-L1 blocking peptide-photosensitizer conjugate enables efficient photothermal显示文摘Mild photothermal therapy combined with immune checkpoint blockade has received increasing attention for the treatment of advanced or metastatic cancers due to its good therapeutic efficacy.However,it remains a challenge to facilely integrate the two therapies and make it potential for clinical translation.This work designed a peptide-photosensitizer conjugate(PPC),which consisted of a PD-L1 antagonist peptide(CVRARTR),an MMP-2 specific cleavable sequence,a self-assembling motif,and the photosensitizer Purpurin 18.The single-component PPC can self-assemble into nanospheres which is suitable for intravenous injection.The PPC nanosphere is cleaved by MMP-2 when it accumulates in tumor sites,thereby initiating the cancer-specific release of the antagonist peptide.Simultaneously,the nanospheres gradually transform into co-assembled nanofibers,which promotes the retention of the remaining parts within the tumor.In vivo studies demonstrated that PPC nanospheres under laser irradiation promote the infiltration of cytotoxic T lymphocytes and maturation of DCs,which sensitize 4T1 tumor cells to immune checkpoint blockade therapy.Therefore,PPC nanospheres inhibit tumor growth efficiently both in situ and distally and blocked the formation of lung metastases.The present study provides a simple and efficient integrated strategy for breast cancer photoimmunotherapy. | Yanan Sun Bochen Lyu Chang Yang Bing He Hua Zhang Xueqing Wang Qiang Zhang Wenbing Dai | 2023 | Bioactive Materials2023，，4： | 4 |
| 2 | Small GTPases:Structure,biological function and its interaction with nanoparticles显示文摘Small GTPase is a kind of GTP-binding protein commonly found in eukaryotic cells.It plays an important role in cytoskeletal reorganization,cell polarity,cell cycle progression,gene expression and many other significant events in cells,such as the interaction with foreign particles.Therefore,it is of great scientific significance to understand the biological properties of small GTPases as well as the GTPase-nano interplay,since more and more nanomedicine are supposed to be used in biomedical field.However,there is no review in this aspect.This review summarizes the small GTPases in terms of the structure,biological function and its interaction with nanoparticles.We briefly introduced the various nanoparticles such as gold/silver nanoparticles,SWCNT,polymeric micelles and other nano delivery systems that interacted with different GTPases.These current nanoparticles exhibited different pharmacological effect modes and various target design concepts in the small GTPases study.This will help to elucidate the conclusion that the therapeutic strategy targeting small GTPases might be a new research direction.It is believed that the in-depth study on the functional mechanism of GTPases can provide insights for the design and study of nanomedicines. | Siyang Song Wenshu Cong Shurong Zhou Yujie Shi Wenbing Dai Hua Zhang Xueqing Wang Bing He Qiang Zhang | 2019 | Asian Journal of Pharmaceutical Sciences2019，14，1： | 3 |
| 3 | The role of caveolin-1 in the biofate and efficacy of anti-tumor drugs and their nano-drug delivery systems显示文摘As one of the most important components of caveolae,caveolin-1 is involved in caveolaemediated endocytosis and transcytosis pathways,and also plays a role in regulating the cell membrane cholesterol homeostasis and mediating signal transduction.In recent years,the relationship between the expression level of caveolin-1 in the tumor microenvironment and the prognostic effect of tumor treatment and drug treatment resistance has also been widely explored.In addition,the interplay between caveolin-1 and nano-drugs is bidirectional.Caveolin-1 could determine the intracellular biofate of specifc nano-drugs,preventing from lysosomal degradation,and facilitate them penetrate into deeper site of tumors by transcytosis;while some nanocarriers could also affect caveolin-1 levels in tumor cells,thereby changing certain biophysical function of cells.This article reviews the role of caveolin-1 in tumor prognosis,chemotherapeutic drug resistance,antibody drug sensitivity,and nano-drug delivery,providing a reference for the further application of caveolin-1 in nano-drug delivery systems. | Canyu Yang Bing He Wenbing Dai Hua Zhang Ying Zheng Xueqing Wang Qiang Zhang | 2021 | Acta Pharmaceutica Sinica B2021，11，4： | 2 |
| 4 | Advances in the formulation and defivery technology of paclitaxel for injection显示文摘紫杉醇用于治疗人体各种实体瘤比如卵巢癌,乳腺癌,头颈部癌和黑色素瘤,是一个很有前景的抗癌药物。由于它的疏水性,紫杉醇的第一个给药剂型泰素是以非水浓缩液的形式存在,成分主要含有聚氧乙烯蓖麻油和乙醇,它在长时间的输注前必须用合适的水溶液稀释。基于它的成分和用法,泰素存在严重的不良反应并造成临床应用的不便。为了解决以上问题,科学家们开始致力于开发低毒、较好耐受性、不含聚氧乙烯蓖麻油的紫杉醇新剂型。最近几年,新的药物递送系统如白蛋白纳米粒、胶束、脂质体等已经处于研究中。在这篇综述中,我们提出了注射用紫杉醇的一些新剂型及递送技术,并且重点研究已经上市的或处于临床研究阶段的几个制剂的部分临床前和临床研究成果。最后,阐述纳米技术优势的几个原因及紫杉醇给药系统现存的挑战和展望。 | Jing Sun Wenbing Dai Zhe Liang Zhaoyang wang Changsheng Huang Bing He Hua Zhang Xueqing Wang Qiang Zhang | 2015 | Journal of Chinese Pharmaceutical Sciences2015，24，8： | 2 |
| 5 | Peptide PHSCNK as an integrin α 5 β 1 antagonist targets stealth liposomes to integrin-overexpressing melanoma显示文摘 | Wenbing Dai Tingyuan Yang Yiguang Wang Xueqing Wang Jiancheng Wang Xuan Zhang Qiang Zhang | 2012 | Nanomedicine: Nanotechnology, Biology, and Medicine2012，，7： | 1 |
| 6 | The transport mechanisms of polymer nanoparticles in Caco-2 epithelial cells显示文摘 | Bing He Ping Lin Zengrong Jia Wenwen Du Wei Qu Lan Yuan Wenbing Dai Hua Zhang Xueqing Wang Jiancheng Wang Xuan Zhang Qiang Zhang | 2013 | Biomaterials2013，，25： | 1 |
| 7 | A biomimetic antitumor nanovaccine based on biocompatible calcium pyrophosphate and tumor cell membrane antigens显示文摘Currently,the cancer immunotherapy has made great progress while antitumor vaccine attracts substantial attention.Still,the selection of adjuvants as well as antigens are always the most crucial issues for better vaccination.In this study,we proposed a biomimetic antitumor nanovaccine based on biocompatible nanocarriers and tumor cell membrane antigens.Briefly,endogenous calcium pyrophosphate nanogranules with possible immune potentiating effect are designed and engineered,both as delivery vehicles and adjuvants.Then,these nanocarriers are coated with lipids and B16-OVA tumor cell membranes,so the biomembrane proteins can serve as tumor-specific antigens.It was found that calcium pyrophosphate nanogranules themselves were compatible and possessed adjuvant effect,while membrane proteins including tumor associated antigen were transferred onto the nanocarriers.It was demonstrated that such a biomimetic nanovaccine could be well endocytosed by dendritic cells,promote their maturation and antigen-presentation,facilitate lymph retention,and trigger obvious immune response.It was confirmed that the biomimetic vaccine could induce strong T-cell response,exhibit excellent tumor therapy and prophylactic effects,and simultaneously possess nice biocompatibility.In general,the present investigation might provide insights for the further design and application of antitumor vaccines. | Minghui Li Mengmeng Qin Ge Song Hailiang Deng Dakuan Wang Xueqing Wang Wenbing Dai Bing He Hua Zhang Qiang Zhang | 2021 | Asian Journal of Pharmaceutical Sciences2021，16，1： | 1 |
| 8 | Optimize the combination regimen of Trastuzumab and Nab-paclitaxel in HER2-positive tumors via modulating Caveolin-1 expression by lovastatin显示文摘The combination regimen of trastuzumab(Tras)plus Nab-paclitaxel(Nab)is recommended to treat HER2-positive(HER2+)cancers.However,they exert effects in different mechanisms:Tras need to stay on cell membranes,while Nab need to be endocytosed,therefore the concurrent combination regimen may not be the best one in HER2+tumors treatment.Caveolin-1(Cav-1)is a key player in mediating their endocytosis and is associated with their efficacy,but few researches noticed the opposite effect of Cav-1 expression on the combination efficacy.Herein,we systematically studied the Cav-1 expression level on the combination efficacy and proposed an optimized and clinically feasible combination regimen for HER2+Cav-1 High tumor treatment.In the regimen,lovastatin(Lova)was introduced to modulate the Cav-1 expression and the results indicated that Lova could downregulate Cav-1 expression,increase Tras retention on cell membrane and enhance the in vitro cytotoxicity of Tras in HER2+Cav-1 High cells but not in HER2+Cav-1 Low cells.Therefore,by exchanging the dosing sequence of Nab and Tras,and by adding Lova at appropriate time points,the precise three-drug-sequential regimen(PTDS,Nab(D1)-Lova(D2)-Lova&Tras(D2+12 h))was established.Compared with the concurrent regimen,the PTDS regimen exhibited a higher in vitro cytotoxicity and a stronger tumor growth inhibition in HER2+Cav-1 High tumors,which might be a promising combination regimen for these patients in clinics. | Canyu Yang Shumin Fan Xing Wang Wei Liu Long Yang Bing He Wenbing Dai Hua Zhang Xueqing Wang Qiang Zhang | 2022 | Asian Journal of Pharmaceutical Sciences2022，17，5： | 0 |
| 9 | Molecular Mechanisms of Intracellular Delivery of Nanoparticles Monitored by an Enzyme‑Induced Proximity Labeling显示文摘Achieving increasingly finely targeted drug delivery to organs,tissues,cells,and even to intracellular biomacromolecules is one of the core goals of nanomedicines.As the delivery destination is refined to cellular and subcellular targets,it is essential to explore the delivery of nanomedicines at the molecular level.However,due to the lack of technical methods,the molecular mechanism of the intracellular delivery of nanomedicines remains unclear to date.Here,we develop an enzyme-induced proximity labeling technology in nanoparticles(nano-EPL)for the real-time monitoring of proteins that interact with intracellular nanomedicines.Poly(lactic-co-glycolic acid)nanoparticles coupled with horseradish peroxidase(HRP)were fabricated as a model(HRP(+)-PNPs)to evaluate the molecular mechanism of nano delivery in macrophages.By adding the labeling probe biotin-phenol and the catalytic substrate H_(2)O_(2)at different time points in cellular delivery,nano-EPL technology was validated for the real-time in situ labeling of proteins interacting with nanoparticles.Nano-EPL achieves the dynamic molecular profiling of 740 proteins to map the intracellular delivery of HRP(+)-PNPs in macrophages over time.Based on dynamic clustering analysis of these proteins,we further discovered that different organelles,including endosomes,lysosomes,the endoplasmic reticulum,and the Golgi apparatus,are involved in delivery with distinct participation timelines.More importantly,the engagement of these organelles differentially affects the drug delivery efficiency,reflecting the spatial–temporal heterogeneity of nano delivery in cells.In summary,these findings highlight a significant methodological advance toward understanding the molecular mechanisms involved in the intracellular delivery of nanomedicines. | Junji Ren Zibin Zhang Shuo Geng Yuxi Cheng Huize Han Zhipu Fan Wenbing Dai Hua Zhang Xueqing Wang Qiang Zhang Bing He | 2024 | Nano-Micro Letters2024，16，6： | 0 |
| 10 | Sperm cryopreservation in the human sperm bank:11-year results of the Chinese mainland sperm banking network显示文摘To the Editor:Montegazza in 1866 was the first to suggest banks for frozen human semen.[1]In 1981,China's first human sperm bank was successfully established at the CITIC Xiangya Hospital.During the previous four decades,from 1981 to 2020,there were 27 human sperm banks in Chinese mainland.Human sperm banks provide cryopreservation of spermatozoa services for males needing to preserve fertility for an extended period in the Chinese mainland. | Xiao Liu Qiling Wang Wenbing Zhu Zhou Zhang Wenhao Tang Huiqiang Sheng Jigao Yang Yushan Li Xiaowei Liang Tianqing Meng Zhiqiang Wang Faxi Lin Hao Dong Xiaojin He Xianglong Jiang Shanjun Dai Aiping Zhang Chunying Song Zuowen Liang Feng Zhang Xiaojun Wang Peiyu Liang Guihua Gong Xiaohong Huai Fuping Xinzong Zhang | 2022 | Chinese Medical Journal2022，135，22： | 0 |
| 11 | Boosting synergism of chemo- and immunotherapies via switching paclitaxel-induced apoptosis to mevalonate metabolism-triggered ferroptosis by bisphosphonate coordination lipid nanogranules显示文摘Conventional chemotherapy based on cytotoxic drugs is facing tough challenges recently following the advances of monoclonal antibodies and molecularly targeted drugs.It is critical to inspire new potential to remodel the value of this classical therapeutic strategy.Here,we fabricate bisphosphonate coordination lipid nanogranules(BC-LNPs)and load paclitaxel(PTX)to boost the chemo-and immuno-therapeutic synergism of cytotoxic drugs.Alendronate in BC-LNPs@PTX,a bisphosphonate to block mevalonate metabolism,works as both the structure and drug constituent in nanogranules,where alendronate coordinated with calcium ions to form the particle core.The synergy of alendronate enhances the efficacy of paclitaxel,suppresses tumor metastasis,and alters the cytotoxic mechanism.Differing from the paclitaxel-induced apoptosis,the involvement of alendronate inhibits the mevalonate metabolism,changes the mitochondrial morphology,disturbs the redox homeostasis,and causes theaccumulation of mitochondrial ROS and lethal lipid peroxides(LPO).These factors finally trigger the ferroptosis of tumor cells,an immunogenic cell death mode,which remodels the suppressive tumor immune microenvironment and synergizes with immunotherapy.Therefore,by switching paclitaxel-induced apoptosis to mevalonate metabolism-triggered ferroptosis,BC-LNPs@PTX provides new insight into the development of cytotoxic drugs and highlights the potential of metabolism regulation in cancer therapy. | Ge Song Minghui Li Shumin Fan Mengmeng Qin Bin Shao Wenbing Dai Hua Zhang Xueqing Wang Bing He Qiang Zhang | 2024 | Acta Pharmaceutica Sinica B2024，14，2： | 0 |
| 12 | One-pot preparation of nanodispersion with readily available components for localized tumor photothermal and photodynamic therapy显示文摘Photothermal(PTT) and photodynamic(PDT) combined therapy has been hindered to clinical translation, due to the lack of available biomaterials, difficult designs of functions,and complex chemical synthetic or preparation procedures. To actualize a high-efficiency combination therapy for cancer via a feasible approach, three readily available materials are simply associated together in one-pot, namely the single-walled carbon nanohorns(SWCNH), zinc phthalocyanine(ZnPc), and surfactant TPGS. The established nanodispersion is recorded as PCT. The association of SWCNH/ZnPc/TPGS was confirmed by energy dispersive spectrum, Raman spectrum and thermogravimetric analysis. Under lighting, PCT induced a temperature rising up to about 60 ℃ due to the presence of SWCNH, production a 7-folds of singlet oxygen level elevation because of ZnPc, which destroyed almost all4T1 tumor cells in vitro. The photothermal effect of PCT depended on both laser intensity and nanodispersion concentration in a linear and nonlinear manner, respectively. After a single peritumoral injection in mice and laser treatment, PCT exhibited the highest tumor temperature rise(to 65 ℃) among all test groups, completely destroyed primary tumor without obvious toxicity, and inhibited distant site tumor. Generally, this study demonstrated the high potential of PCT nanodispersion in tumor combined therapy. | Anpu Yang Yanan Sun Bochen Lyu Binlong Chen Zhipu Fan Minghui Li Yao Zhao Jijun Fu Bing He Hua Zhang Xueqing Wang Wenbing Dai Qiang Zhang | 2022 | Asian Journal of Pharmaceutical Sciences2022，17，1： | 0 |
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