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Issue 24, 2018
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An autonomous tumor-targeted nanoprodrug for reactive oxygen species-activatable dual-cytochrome c/doxorubicin antitumor therapy

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Abstract

The precise tumor cell-specific delivery of therapeutic proteins and the elimination of side effects associated with routine chemotherapeutic agents are two current critical considerations for tumor therapy. In this study, we report a reactive oxygen species (ROS)-activated yolk–shell nanoplatform for the tumor-specific co-delivery of cytochrome c (Cyt c) prodrug and doxorubicin, in which the bioactivity of Cyt c could be restored by the intracellular ROS-trigger and readily initiate the sequential doxorubicin release. The DOX-loaded lactobionic acid-modified yolk–shell mesoporous silica nanoparticles were first encapsulated with 4-nitrophenyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl carbonate (NBC)-modified Cyt c via boronic ester linkages, and functionalized again with lactobionic acid to further shield Cyt c and confer the selective tumor targeting against liver cancer cells. The key feature in this design is that by taking advantage of the boronic ester linkage, the cytotoxicity of Cyt c capped on the nanoparticle could be temporarily deactivated during blood transportation and rapidly restored upon exposure to the ROS-rich microenvironment within liver cancer cells, thereby simultaneously achieving the protein therapy and stimuli-responsive doxorubicin release. This study presents a novel strategy for the development of tumor-sensitive co-delivery nanoplatforms.

Graphical abstract: An autonomous tumor-targeted nanoprodrug for reactive oxygen species-activatable dual-cytochrome c/doxorubicin antitumor therapy

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Publication details

The article was received on 22 Mar 2018, accepted on 26 Apr 2018 and first published on 03 May 2018


Article type: Paper
DOI: 10.1039/C8NR02358A
Nanoscale, 2018,10, 11418-11429

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    An autonomous tumor-targeted nanoprodrug for reactive oxygen species-activatable dual-cytochrome c/doxorubicin antitumor therapy

    Y. Pei, M. Li, Y. Hou, Y. Hu, G. Chu, L. Dai, K. Li, Y. Xing, B. Tao, Y. Yu, C. Xue, Y. He, Z. Luo and K. Cai, Nanoscale, 2018, 10, 11418
    DOI: 10.1039/C8NR02358A

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