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| 1 | Erythrocyte membrane-camouflaged carrier-free nanoassembly of FRET photosensitizer pairs with high therapeutic efficiency and high security for programmed cancer synergistic phototherapy显示文摘Phototherapy has been intensively investigated as a non-invasive cancer treatment option.However,its clinical translation is still impeded by unsatisfactory therapeutic efficacy and severe phototoxicity.To achieve high therapeutic efficiency and high security,a nanoassembly of Forster Resonance Energy Transfer(FRET)photosensitizer pairs is developed on basis of dual-mode photosensitizer co-loading and photocaging strategy.For proof-of-concept,an erythrocyte-camouflaged FRET pair co-assembly of chlorine e6(Ce6,FRET donor)and 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindotricarbocyanine iodide(DiR,FRET acceptor)is investigated for breast cancer treatment.Notably,Ce6 in the nanoassemby is quenched by DiR and could be unlocked for photodynamic therapy(PDT)only when DiR is photobleached by 808-nm laser.As a result,Ce6-caused phototoxicity could be well controlled.Under cascaded laser irradiation(808-660 nm),tumor-localizing temperature rise following laser irradiation on DiR not only induces tumor cell apoptosis but also facilitates the tumor penetration of NPs,relieves tumor hypoxia,and promotes the PDT efficacy of Ce6.Such FRET pair-based nanoassembly provides a new strategy for developing multimodal phototherapy nanomedicines with high efficiency and good security. | Xuanbo Zhang Jianchen Xiong Kaiyuan Wang Han Yu Bingjun Sun Hao Ye Zhiqiang Zhao Ning Wang Yuequan Wang Shenwu Zhang Wutong Zhao Haotian Zhang Zhonggui He Cong Luo Jin Sun | 2021 | Bioactive Materials2021，6，8： | 4 |
| 2 | Pure photosensitizer-driven nanoassembly with core-matched PEGylation for imaging-guided photodynamic therapy显示文摘Pure drug-assembled nanomedicines(PDANs)are currently under intensive investigation as promising nanoplatforms for cancer therapy.However,poor colloidal stability and less tumor-homing ability remain critical unresolved problems that impede their clinical translation.Herein,we report a core-matched nanoassembly of pyropheophorbide a(PPa)for photodynamic therapy(PDT).Pure PPa molecules are found to self-assemble into nanoparticles(NPs),and an amphiphilic PEG polymer(PPaPEG_(2K))is utilized to achieve core-matched PEGylating modification via the p-p stacking effect and hydrophobic interaction between the PPa core and the PPa-PEG_(2K) shell.Compared to PCL-PEG_(2K) with similar molecular weight,PPa-PEG_(2K) significantly increases the stability,prolongs the systemic circulation and improves the tumor-homing ability and ROS generation efficiency of PPa-nanoassembly.As a result,PPa/PPa-PEG_(2K) NPs exert potent antitumor activity in a 4T1 breast tumor-bearing BALB/c mouse xenograft model.Together,such a core-matched nanoassembly of pure photosensitizer provides a new strategy for the development of imaging-guided theragnostic nanomedicines. | Shenwu Zhang Yuequan Wang Zhiqiang Kong Xuanbo Zhang Bingjun Sun Han Yu Qin Chen Cong Luo Jin Sun Zhonggui He | 2021 | Acta Pharmaceutica Sinica B2021，11，11： | 3 |
| 3 | Construction of the Chinese Veteran Clinical Research (CVCR) Platform for the assessment of non-communicable diseases显示文摘 | Tan Jiping Li Nan Gao Jing Guo Yuhe Hu Wei Yang Jinsheng Yu Baocheng Yu Jianmin Du Wei Zhang Wenjun Cui Lianqi Wang Qingsong Xia Xiangnan Li Jianjun Zhou Peiyi Zhang Baohe Liu Zhiying Zhang Shaogang Sun Lanying Liu Nan Deng Ruixiang Dai Wenguang Yi Fang Chen Wenjun Zhang Yongqing Xue Shenwu Cui Bo Zhao Yiming Wang Luning | 2014 | Chinese Medical Journal2014，，3： | 3 |
| 4 | Oxidation-strengthened disulfide-bridged prodrug nanoplatforms with cascade facilitated drug release for synergetic photochemotherapy显示文摘One of the major barriers in utilizing prodrug nanocarriers for cancer therapy is the slow release of parent drug in tumors.Tumor cells generally display the higher oxidative level than normal cells,and also displayed the heterogeneity in terms of redox homeostasis level.We previously found that the disulfide bond-linkage demonstrates surprising oxidationsensitivity to form the hydrophilic sulfoxide and sulphone groups.Herein,we develop oxidation-strengthened prodrug nanosystem loaded with pyropheophorbide a(PPa)to achieve light-activatable cascade drug release and enhance therapeutic efficacy.The disulfide bond-driven prodrug nanosystems not only respond to the redox-heterogeneity in tumor,but also respond to the exogenous oxidant(singlet oxygen)elicited by photosensitizers.Once the prodrug nanoparticles(NPs)are activated under irradiation,they would undergo an oxidative self-strengthened process,resulting in a facilitated drug cascade release.The IC50 value of the PPa@PTX-S-S NPs without irradiation was 2-fold higher than those of NPs plus irradiation.In vivo,the PPa@PTX prodrug NPs display prolonged systemic circulation and increased accumulation in tumor site.The PPa@PTXS-S NPs showed much higher efficiency than free PTX or the PPa@PTX-C-C NPs to suppress the growth of 4 T1 tumors.Therefore,this novel oxidation-strengthened disulfide-bridged prodrug-nanosystem has a great potential in the enhanced efficacy of cancer synergetic photochemotherapy. | Bin Yang Lin Wei Yuequan Wang Na Li Bin Ji Kaiyuan Wang Xuanbo Zhang Shenwu Zhang Shuang Zhou Xiaohui Yao Hang Song Yusheng Wu Haotian Zhang Qiming Kan Tao Jin Jin Sun | 2020 | Asian Journal of Pharmaceutical Sciences2020，15，5： | 2 |
| 5 | Elaborately engineering of a dual-drug co-assembled nanomedicine for boosting immunogenic cell death and enhancing triple negative breast cancer treatment显示文摘Pure drug-assembled nanosystem provides a facile and promising solution for simple manufacturing of nanodrugs,whereas a lack of understanding of the underlying assembly mechanism and the inefficient and uncontrollable drug release still limits the development and application of this technology.Here,a simple and practical nanoassembly of DOX and DiR is constructed on basis of their co-assembly characteristics.Multiple interaction forces are found to drive the co-assembly process.Moreover,DOX release from the nanoassembly can bewell controlled by the acidic tumormicroenvironment and laser irradiation,resulting in favorable delivery efficiency of DiR and DOX in vitro and in vivo.As expected,the nanoassembly with high therapeutic safety completely eradicated the mice triple negative breast cancer cells(4T1)on BALB/c mice,owing to synergistic chemo-photothermal therapy.More interestingly,DiR and DOX synergistically induce immunogenic cell death(ICD)of tumor cells after treatment,enabling the mice to acquire immune memory against tumor growth and recurrence.Such a facile nanoassembly technique provides a novelmultimodal cancer treatment platform of chemotherapy/phototherapy/immunotherapy. | Chen Wang Han Yu Xiaohong Yang Xuanbo Zhang Yuequan Wang Tianrui Gu Shenwu Zhang Cong Luo | 2022 | Asian Journal of Pharmaceutical Sciences2022，17，3： | 1 |
| 6 | Precisely engineering a dual-drug cooperative nanoassembly for proteasome inhibition-potentiated photodynamic therapy显示文摘Photodynamic therapy(PDT) has been widely investigated for cancer therapy. The intracellular accumulation of reactive oxygen species(ROS)-damaged protein facilitates tumor cell apoptosis. However, there is growing evidence that the ubiquitin-proteasome pathway(UPP) significantly impedes PDT by preventing the enrichment of ROS-damaged proteins in tumor cells. To tackle this challenge, we report a facile dual-drug nanoassembly based on the discovery of an interesting co-assembly of bortezomib(BTZ, a proteasome inhibitor) and pyropheophorbide a(PPa) for proteasome inhibition-mediated PDT sensitization.The precisely engineered nanoassembly with the optimal dose ratio of BTZ and PPa demonstrates multiple advantages, including simple fabrication, high drug co-loading efficiency, flexible dose adjustment,good colloidal stability, long systemic circulation, favorable tumor-specific accumulation, as well as significant enrichment of ROS-damaged proteins in tumor cells. As a result, the cooperative nanoassembly exhibits potent synergistic antitumor activity in vivo. This study provides a novel dual-drug engineering modality for multimodal cancer treatment. | Fujun Yang Qingyu Ji Rui Liao Shumeng Li Yuequan Wang Xuanbo Zhang Shenwu Zhang Haotian Zhang Qiming Kan Jin Sun Zhonggui He Bingjun Sun Cong Luo | 2022 | Chinese Chemical Letters2022，33，4： | 1 |
| 7 | Modularly engineered prodrug-nanoassemblies for cancer therapy:Nonpharmacological moiety dominating delivery fates显示文摘Self-engineered small-molecule prodrug-nanoassemblies have emerged as promising nanomedicines for cancer treatment.Modular design of prodrug molecules is crucial to guarantee the favorable assembly stability,tumor-specific prodrug activation,and satisfactory antitumor effect.However,too much attention has been paid to the pharmacophores and chemical linkages in prodrug molecules while neglects the vital roles of nonpharmacological moieties.Herein,we found that iso-carbon fatty acids with different number,position,and cis-trans configuration of double bonds dramatically affect the nanoassembly feature and drug delivery fates of thioether-linked paclitaxel prodrug-nanoassemblies.Particularly,the number and cis-trans configuration of double bonds in fatty acid moieties not only dominate the self-assembly ability and colloidal stability of prodrugs,but also exert significant influences on the pharmacokinetics,prodrug activation,and antitumor activity of prodrug-nanoassemblies.Finally,oleic acid with one cis double bond stands out as the optimal nonpharmacological moiety for thioether-linked paclitaxel prodrugnanoassemblies.This study elucidates the crucial roles of nonpharmacological moieties in prodrugs,and provides new insights into the modular design of prodrug-based nanomedicines for cancer therapy. | Yuequan Wang Qian Qiu Rui Liao Xinhui Wang Ziran Zhou Xuanbo Zhang Haotian Zhang Zhonggui He Shenwu Zhang Cong Luo Jin Sun | 2023 | Nano Research2023，16，1： | 0 |
| 8 | Investigating the crucial roles of aliphatic tails in disulfide bond-linked docetaxel prodrug nanoassemblies显示文摘Disulfide bond-bridging strategy has been extensively utilized to construct tumor specificity-responsive aliphatic prodrug nanoparticles(PNPs) for precise cancer therapy. Yet, there is no research shedding light on the impacts of the saturation and cis-trans configuration of aliphatic tails on the self-assembly capacity of disulfide bond-linked prodrugs and the in vivo delivery fate of PNPs. Herein, five disulfide bond-linked docetaxelfatty acid prodrugs are designed and synthesized by using stearic acid, elaidic acid, oleic acid, linoleic acid and linolenic acid as the aliphatic tails, respectively. Interestingly, the cistrans configuration of aliphatic tails significantly influences the self-assembly features of prodrugs, and elaidic acid-linked prodrug with a trans double bond show poor self-assembly capacity. Although the aliphatic tails have almost no effect on the redox-sensitive drug release and cytotoxicity, different aliphatic tails significantly influence the chemical stability of prodrugs and the colloidal stability of PNPs, thus affecting the in vivo pharmacokinetics, biodistribution and antitumor efficacy of PNPs. Our findings illustrate how aliphatic tails affect the assembly characteristic of disulfide bond-linked aliphatic prodrugs and the in vivo delivery fate of PNPs, and thus provide theoretical basis for future development of disulfide bond-bridged aliphatic prodrugs. | Yuequan Wang Cong Luo Shuang Zhou Xinhui Wang Xuanbo Zhang Shumeng Li Shenwu Zhang Shuo Wang Bingjun Sun Zhonggui He Jin Sun | 2021 | Asian Journal of Pharmaceutical Sciences2021，16，5： | 0 |
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