3 years ago

Transformative Nanomedicine of an Amphiphilic Camptothecin Prodrug for Long Circulation and High Tumor Uptake in Cancer Therapy

Transformative Nanomedicine of an Amphiphilic Camptothecin Prodrug for Long Circulation and High Tumor Uptake in Cancer Therapy
Qianqian Ni, Fuwu Zhang, Frederick Xu, Orit Jacobson, Zhe Wang, Jing Fan, Guocan Yu, Guizhi Zhu, Ying Ma, Xiao Fu, Zhen Yang, Xiaobin Zhao, Gang Niu, Yi Liu, Xiaoyuan Chen, Kai Chen
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.

Publisher URL: http://dx.doi.org/10.1021/acsnano.7b03003

DOI: 10.1021/acsnano.7b03003

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