Issue 24, 2018

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

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

Supplementary files

Article information

Article type
Paper
Submitted
22 мар 2018
Accepted
26 апр 2018
First published
03 май 2018

Nanoscale, 2018,10, 11418-11429

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

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements