文献类型：期刊文献

英文题名：Self-accelerating H2O2-responsive Plasmonic Nanovesicles for Synergistic Chemo/starving therapy of Tumors

作者：Tang, Yao[1];Ji, Yuejia[1];Yi, Chenglin[2];Cheng, Di[1];Wang, Bin[1];Fu, Yun[1];Xu, Yufang[1];Qian, Xuhong[1];Choonara, Yahya E.[3];Pillay, Viness[3];Zhu, Weiping[1];Liu, Yunen[4];Nie, Zhihong[2]

机构：[1]East China Univ Sci & Technol, Sch Pharm, State Key Lab Bioreactor Engn, Shanghai Key Lab Chem Biol, Shanghai 200237, Peoples R China;[2]Fudan Univ, Dept Macromol Sci, State Key Lab Mol Engn Polymers, Shanghai 200438, Peoples R China;[3]Univ Witwatersrand, Dept Pharm & Pharmacol, ZA-2193 Johannesburg, South Africa;[4]Gen Hosp Northern Theater Command, Lab Rescue Ctr Severe Trauma PLA, Dept Emergency Med, Shenyang 110016, Peoples R China

年份：2020

卷号：10

期号：19

起止页码：8691

外文期刊名：THERANOSTICS

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000548566600004)】；

基金：This work was supported by the grants from the National Natural Science Foundation of China (Grants 21878088, 21476077, 21236002, 51973038), Key Project of the Shanghai Science and Technology Committee (18DZ1112703) and PLA Foundation of China (Grants BWS16J010, AWS14L008, CSY13J003).

语种：英文

外文关键词：hydrogen peroxide; gold vesicles; cancer therapy; controlled release; cancer imaging; self-accelerating

摘要：Rationale: Nanoscale vehicles responsive to abnormal variation in tumor environment are promising for use in targeted delivery of therapeutic drugs specifically to tumor sites. Herein, we report the design and fabrication of self-accelerating H2O2-responsive plasmonic gold nanovesicles (GVs) encapsulated with tirapazamine (TPZ) and glucose oxidase (GOx) for synergistic chemo/starving therapy of cancers. Methods: Gold nanoparticles were modified with H2O2-responsive amphiphilic block copolymer PEG(45)-b-PABE(330) by ligand exchange. The TPZ and GOx loaded GVs (TG-GVs) were prepared through the self-assembly of PEG(45)-b-PABE(330)-grafted nanoparticles together with TPZ and GOx by solvent displacement method. Results: In response to H2O2 in tumor, the TG-GVs dissociate to release the payloads that are, otherwise, retained inside the vesicles for days without noticeable leakage. The released GOx enzymes catalyze the oxidation of glucose by oxygen in the tumor tissue to enhance the degree of hypoxia that subsequently triggers the reduction of hypoxia-activated pro-drug TPZ into highly toxic free radicals. The H2O2 generated in the GOx-catalyzed reaction also accelerate the dissociation of vesicles and hence the release rate of the cargoes in tumors. The drug-loaded GVs exhibit superior tumor inhibition efficacy in 4T1 tumor-bearing mice owing to the synergistic effect of chemo/starvation therapy, in addition to their use as contrast agents for computed tomography imaging of tumors. Conclusion: This nanoplatform may find application in managing tumors deeply trapped in viscera or other important tissues that are not compatible with external stimulus (e.g. light).