Quadruple-responsive nanoparticle-mediated targeted combination chemotherapy for metastatic breast cancer
- 29 January 2021
- journal article
- research article
- Published by Royal Society of Chemistry (RSC) in Nanoscale
- Vol. 13 (11), 5765-5779
- https://doi.org/10.1039/d0nr08579k
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.Funding Information
- National Natural Science Foundation of China (82072060, 22008201)
- Fundamental Research Funds for the Central Universities (XDJK2019TY002, XDJK2019B016)
- Venture and Innovation Support Program for Chongqing Overseas Returnees (cx2018029)
- Natural Science Foundation of Chongqing (cstc2020jcyj-msxmX0292)
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