Issue 11, 2021

Quadruple-responsive nanoparticle-mediated targeted combination chemotherapy for metastatic breast cancer

Abstract

The synergism of combination chemotherapy can only be achieved under specific drug ratios. Herein, hyaluronic acid (HA)-functionalized regenerated silk fibroin-based nanoparticles (NPs) were used to concurrently deliver curcumin (CUR) and 5-fluorouracil (5-FU) at various weight ratios (3.3 : 1, 1.6 : 1, 1.1 : 1, 1 : 1, and 1 : 1.2) to breast tumor cells. The generated HA-CUR/5-FU-NPs were found to have desirable particle sizes (around 200 nm), narrow size distributions, and negative zeta potentials (about −26.0 mV). Interestingly, these NPs showed accelerated drug release rates when they were exposed to buffers that mimicked the multi-hallmarks in the tumor microenvironment (pH/hydrogen peroxide/glutathione/hyaluronidase). The surface functionalization of NPs with HA endowed them with in vitro and in vivo breast tumor-targeting properties. Furthermore, we found that the co-loading of CUR and 5-FU in HA-functionalized NPs exhibited obvious synergistic anti-cancer, pro-apoptotic, and anti-migration effects, and the strongest synergism was found at the CUR/5-FU weight ratio of 1 : 1.2. Most importantly, mice experiments revealed that HA-CUR/5-FU-NPs (1 : 1.2) showed a superior anti-cancer activity against metastatic breast cancer compared to the single drug-loaded NPs and non-functionalized CUR/5-FU-NPs (1 : 1.2). Collectively, these results demonstrate that HA-CUR/5-FU-NPs (1 : 1.2) can be exploited as a robust nanococktail for the treatment of breast cancer and its lung metastasis.

Graphical abstract: Quadruple-responsive nanoparticle-mediated targeted combination chemotherapy for metastatic breast cancer

Supplementary files

Article information

Article type
Paper
Submitted
03 Dec 2020
Accepted
26 Jan 2021
First published
29 Jan 2021

Nanoscale, 2021,13, 5765-5779

Quadruple-responsive nanoparticle-mediated targeted combination chemotherapy for metastatic breast cancer

Y. Huang, D. Xie, S. Gou, B. S. B. Canup, G. Zhang, F. Dai, C. Li and B. Xiao, Nanoscale, 2021, 13, 5765 DOI: 10.1039/D0NR08579K

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