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Zhang, Fuwu; Zhu, Guizhi; Jacobson, Orit; Liu, Yi; Chen, Kai; Yu, Guocan; Ni, Qianqian; Fan, Jing; Yang, Zhen; Xu, Frederick; Fu, Xiao; Wang, Zhe; Ma, Ying; Niu, Gang; Zhao, Xiaobin; Chen, Xiaoyuan
ACS nano, 09/2017, Volume: 11, Issue: 9Journal Article
We report a camptothecin (CPT) prodrug that was well formulated in solution and rapidly transformed into long-circulating nanocomplexes in vivo for highly efficient drug delivery and effective cancer therapy. Specifically, using a redox-responsive disulfide linker, CPT was conjugated with an albumin-binding Evans blue (EB) derivative; the resulting amphiphilic CPT-ss-EB prodrug self-assembled into nanostructures in aqueous solution, thus conferring high solubility and stability. By binding CPT-ss-EB to endogenous albumin, the 80 nm CPT-ss-EB nanoparticles rapidly transformed into 7 nm albumin/prodrug nanocomplexes. CPT-ss-EB was efficient at intracellular delivery into cancer cells, released intact CPT in a redox-responsive manner, and exhibited cytotoxicity as potent as CPT. In mice, the albumin/CPT-ss-EB nanocomplex exhibited remarkably long blood circulation (130-fold greater than CPT) and efficient tumor accumulation (30-fold of CPT), which consequently contributed to excellent therapeutic efficacy. Overall, this strategy of transformative nanomedicine is promising for efficient drug delivery.
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