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Research Article

A targeted nanoplatform co-delivery of pooled siRNA and doxorubicin for reversing of multidrug resistance in breast cancer

Hongmei Liu1,2,§, Ding Ma3,§, Jinpeng Chen4,§, Li Ye2, Yiping Li5, Yuexia Xie2, Xue Zhao2, Hanbing Zou2, Xiaojing Chen2, Jun Pu1, Peifeng Liu1,2( )
State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200032, China
Central Laboratory, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
Department of Biliary-Pancreatic Surgery, Shanghai Jiao Tong University School of Medicine Affiliated Renji Hospital, Shanghai 200127, China
Thyroid Breast Surgery, Nantong First People’s Hospital, Nantong 226001, China
Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China

§ Hongmei Liu, Ding Ma, and Jinpeng Chen contributed equally to this work.

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Abstract

Multi-drug resistance (MDR) has become the largest obstacle to the success of cancer patients receiving traditional chemotherapeutics or novel targeted drugs. Here, we developed a targeted nanoplatform based on biodegradable boronic acid modified ε-polylysine to co-deliver P-gp siRNA, Bcl-2 siRNA, and doxorubicin for overcoming the challenge. The targeted nanoplatform showed a robust suppressing efficiency for the invasion, proliferation, and colony formation of adriamycin (ADR) resistant breast cancer cell line (MCF-7/ADR) cells in vitro. The ATP responsiveness of the nanoplatform was also proved in the research. In thein vivo antitumor experiment, the targeted nanoplatform showed a significant inhibition of tumor growth with good biocompatibility. The goal of this study is to develop a novel and facile strategy to prepare a highly efficient and safe gene and drug delivery system for MDR breast cancer based on biocompatible ε-polylysine polymers.

Graphical Abstract

In this research, a targeted nanoplatform based on boronic acid modified ε-polylysine was developed to reverse multidrug resistance in adriamycin (ADR) resistant breast cancer. The nanoplatform, co-delivery of P-glycoprotein (P-gp) siRNA, Bcl-2 siRNA, and doxorubicin, showed a robust suppressing efficiency of ADR resistant breast cancer in vitro and in vivo.

Keywords

multi-drug resistance (MDR)breast canceradenosine triphosphate (ATP) responsivenessε-polylysine

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Nano Research
Volume 15 Issue 7,
July 2022
Pages 6306-6314
DOI: 10.1007/s12274-022-4254-1

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Cite this article:
Liu H, Ma D, Chen J, et al. A targeted nanoplatform co-delivery of pooled siRNA and doxorubicin for reversing of multidrug resistance in breast cancer. Nano Research, 2022, 15(7): 6306-6314. https://doi.org/10.1007/s12274-022-4254-1
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Targeted drug delivery

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Received: 06 December 2021
Revised: 17 February 2022
Accepted: 20 February 2022
Published: 18 April 2022
© Tsinghua University Press 2022