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Oxidation-strengthened disulfide-bridged prodrug nanoplatforms with cascade facilitated drug release for synergetic photochemotherapy

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Asian Journal of Pharmaceutical Sciences 2020年第5期15卷 637-645页

作者： 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 Wuya College of Innovation Shenyang Pharmaceutical UniversityShenyang 110016China Ministry of Education Heilongjiang UniversityHarbin 150500China Sino-Russian Joint Graduate School Heilongjiang UniversityHarbin 150080China Department of Laboratory Medicine The First Affiliated HospitalChina Medical UniversityShenyang 110001China School of Life Science and Biopharmaceutics Shenyang Pharmaceutical UniversityShenyang 110016China School of Life Sciences Heilongjiang UniversityHarbin 150080China

One of the major barriers in utilizing prodrug nanocarriers for cancer therapy is the slow release of parent drug in *** cells generally display the higher oxidative level than normal cells,and also displayed the heterogeneity in terms of redox homeostasis *** previously found that the disulfide bond-linkage demonstrates surprising oxidationsensitivity to form the hydrophilic sulfoxide and sulphone ***,we develop oxidation-strengthened prodrug nanosystem loaded with pyropheophorbide a(PPa)to achieve light-activatable cascade drug release and enhance therapeutic *** 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 *** the prodrug nanoparticles(NPs)are activated under irradiation,they would undergo an oxidative self-strengthened process,resulting in a facilitated drug cascade *** IC50 value of the PPa@PTX-S-S NPs without irradiation was 2-fold higher than those of NPs plus *** vivo,the PPa@PTX prodrug NPs display prolonged systemic circulation and increased accumulation in tumor *** 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 ***,this novel oxidation-strengthened disulfide-bridged prodrug-nanosystem has a great potential in the enhanced efficacy of cancer synergetic photochemotherapy.

关键词： Prodrug nanoplatform Disulfide bond Pyropheophorbide a redox-heterogeneity Accurate therapy

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