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| 1 | Small changes in the length of diselenide bond-containing linkages exert great influences on the antitumor activity of docetaxel homodimeric prodrug nanoassemblies显示文摘Homodimeric prodrug-based self-assembled nanoparticles,with carrier-free structure and ultrahigh drug loading,is drawing more and more attentions.Homodimeric prodrugs are composed of two drug molecules and a pivotal linkage.The influence of the linkages on the self-assembly,in vivo fate and antitumor activity of homodimeric prodrugs is the focus of research.Herein,three docetaxel(DTX)homodimeric prodrugs are developed using different lengths of diselenide bond-containing linkages.Interestingly,compared with the other two linkages,the longest diselenide bond-containing linkage could facilitate the self-delivery of DTX prodrugs,thus improving the stability,circulation time and tumor targeting of prodrug nanoassemblies.Besides,the extension of linkages reduces the redox-triggered drug release and cytotoxicity of prodrug nanoassemblies in tumor cells.Although the longest diselenide bond-containing prodrug nanoassemblies possessed the lowest cytotoxicity to 4T1 cells,their stable nanostructure maintained intact during circulation and achieve the maximum accumulation of DTX in tumor cells,which finally“turned the table”.Our study illustrates the crucial role of linkages in homodimeric prodrugs,and gives valuable proposal for the development of advanced nano-DDS for cancer treatment. | Lingxiao Li Shiyi Zuo Fudan Dong Tian Liu Yanlin Gao Yinxian Yang Xin Wang Jin Sun Bingjun Sun Zhonggui He | 2021 | Asian Journal of Pharmaceutical Sciences2021，16，3： | 3 |
| 2 | Minor change in the length of carbon chain has a great influence on the antitumor effect of paclitaxel-fatty alcohol prodrug nanoassemblies:Small roles,big impacts显示文摘Prodrug-based nanoassembly emerges as a hopeful way for the efficient delivery of antitumor drugs,with carrier-free structure and ultra-high drug loading.Carbon chains are widely used to design self-assembling prodrugs.The impacts of the length of carbon chains on the self-assembly stability,drug delivery efficiency and antitumor effect of prodrugs have not been fully elucidated.Here,three paclitaxel prodrugs were synthesized by conjugating paclitaxel with octanol(C_(8)),decanol(C_(10))or dodecanol(C_(12))through disulfide bond.The three prodrugs could form homogeneous nanoparticles,with over 50%drug loading and redox dual-responsivity.Interestingly,the length extension of carbon chains ameliorates the self-assembly and the colloidal stability of prodrugs,thus improving the drug delivery efficiency.The optimal paclitaxel-dodecanol prodrug nanoassemblies exhibit better antitumor efficacy than Taxol and Abraxane.These findings are meaningful for the rational design of advanced nanomedicines in cancer therapy. | Xin Wang Lingxiao Li Danping Wang Shiyi Zuo Tian Liu Fudan Dong Xuanbo Zhang Zhonggui He Bingjun Sun Jin Sun | 2022 | Nano Research2022，15，4： | 1 |
| 3 | Iron-doxorubicin prodrug loaded liposome nanogenerator programs multimodal ferroptosis for efficient cancer therapy显示文摘Ferroptosis is a new mode of cell death,which can be induced by Fenton reactionmediated lipid peroxidation.However,the insufficient H2O2 and high GSH in tumor cells restrict the efficiency of Fenton reaction-dependent ferroptosis.Herein,a self-supplying lipid peroxide nanoreactor was developed to co-delivery of doxorubicin(DOX),iron and unsaturated lipid for efficient ferroptosis.By leveraging the coordination effect between DOX and Fe3+,trisulfide bond-bridged DOX dimeric prodrug was actively loaded into the core of the unsaturated lipids-rich liposome via iron ion gradient method.First,Fe3+could react with the overexpressed GSH in tumor cells,inducing the GSH depletion and Fe2+generation.Second,the cleavage of trisulfide bond could also consume GSH,and the released DOX induces the generation of H2O2,which would react with the generated Fe2+in step one to induce efficient Fenton reaction-dependent ferroptosis.Third,the formed Fe3+/Fe2+couple could directly catalyze peroxidation of unsaturated lipids to boost Fenton reaction-independent ferroptosis.This iron-prodrug liposome nanoreactor precisely programs multimodal ferroptosis by integrating GSH depletion,ROS generation and lipid peroxidation,providing new sights for efficient cancer therapy. | Yinxian Yang Shiyi Zuo Linxiao Li Xiao Kuang Jinbo Li Bingjun Sun Shujun Wang Zhonggui He Jin Sun | 2021 | Asian Journal of Pharmaceutical Sciences2021，16，6： | 1 |
| 4 | Synergetic lethal energy depletion initiated by cancer cell membrane camouflaged nano-inhibitor for cancer therapy显示文摘Mitochondrial bioenergy plays a vital role in the occurrence and development of cancer.Although strategies to impede mitochondrial energy supply have been rapidly developed,the anticancer efficacy is still far from satisfactory,mainly attributed to the hybrid metabolic pathways of mitochondrial oxidative phosphorylation(OXPHOS)and glycolysis.Herein,we construct a cancer cell membrane camouflaged nano-inhibitor,mTPPa-Sy nanoparticle(NP),which co-encapsulates OXPHOS inhibitor(mitochondrial-targeting photosensitizers:TPPa)and glycolysis inhibitor(syrosingopine(Sy))for synergistically blocking the two different energy pathways.The mTPPa-Sy NPs exhibit precision tumor-targeting due to the high affinity between the biomimic membrane and the homotypic cancer cells.Under laser irradiation,the mitochondrial-targeting TPPa,which is synthesized by conjugating pyropheophorbide a(PPa)with triphenylphosphin,produces excessive reactive oxygen species(ROS)and further disrupts the OXPHOS.Interestingly,OXPHOS inhibition reduces O_(2) consumption and improves ROS production,further constructing a closed-loop OXPHOS inhibition system.Moreover,TPPa-initiated OXPHOS inhibition in combination with the Sytriggered glycolysis inhibition results in lethal energy depletion,significantly suppressing tumor growth even after a single treatment.Our findings highlight the necessity and effectiveness of synergetic lethal energy depletion,providing a prospective strategy for efficient cancer therapy. | Fudan Dong Qikun Jiang Lingxiao Li Tian Liu Shiyi Zuo Lin Gao Mengna Fang Yanlin Gao Bingjun Sun Cong Luo Zhonggui He Jin Sun | 2022 | Nano Research2022，15，4： | 0 |
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