Issue 24, 2023

Amphiphilic phosphorous dendron micelles co-deliver microRNA inhibitor and doxorubicin for augmented triple negative breast cancer therapy

Abstract

Combined chemo/gene therapy of cancer through different action mechanisms has been emerging to enhance the therapeutic efficacy towards cancer, and still remains a challenging task due to the lack of highly effective and biocompatible nanocarriers. In this work, we report a new nanosystem based on amphiphilic phosphorus dendron (1-C12G1) micelles to co-deliver microRNA-21 inhibitor (miR-21i) and doxorubicin (DOX) for combination therapy of triple negative breast cancer. The amphiphilic phosphorus dendron bearing a long linear alkyl chain and ten protonated pyrrolidine surface groups was prepared and was demonstrated to form micelles in water solution and have a hydrodynamic size of 103.2 nm. The micelles are shown to be stable, enable encapsulation of an anticancer drug DOX with optimal loading content (80%) and encapsulation efficiency (98%), and can compress miR-21i to form polyplexes to render it with good stability against degradation. The co-delivery system of 1-C12G1@DOX/miR-21i polyplexes has a pH-dependent DOX release profile, and can be readily phagocytosed by cancer cells to inhibit them due to the different anticancer mechanisms, which was further validated after intravenous injection to treat an orthotopic triple-negative breast tumor model in vivo. With the proven biocompatibility under the studied doses, the developed amphiphilic phosphorus dendron micelles could be developed as an effective nanomedicine formulation for synergistic cancer therapy.

Graphical abstract: Amphiphilic phosphorous dendron micelles co-deliver microRNA inhibitor and doxorubicin for augmented triple negative breast cancer therapy

Supplementary files

Article information

Article type
Paper
Submitted
04 okt 2022
Accepted
22 noy 2022
First published
23 noy 2022

J. Mater. Chem. B, 2023,11, 5483-5493

Amphiphilic phosphorous dendron micelles co-deliver microRNA inhibitor and doxorubicin for augmented triple negative breast cancer therapy

L. Chen, M. Zhan, J. Li, L. Cao, H. Sun, R. Laurent, S. Mignani, A. Caminade, J. Majoral and X. Shi, J. Mater. Chem. B, 2023, 11, 5483 DOI: 10.1039/D2TB02114E

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