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Recent Patents on Anti-Cancer Drug Discovery

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ISSN (Print): 1574-8928
ISSN (Online): 2212-3970

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Research Article

pH-responsive Sulfated Hyaluronic Acid Nanoparticles Targeting Tumor Cells and CAFs for the Treatment of Breast Cancer

Author(s): Di Wang, Jingliang Wu, Cuiping Qi, Jinping Dong, Xueying Ding, Guohua Yu, Shuzhen Liu, Bo Zhang, Zhiqin Gao, Xiuhong Wei* and Hongying Liu*

Volume 18, Issue 2, 2023

Published on: 04 August, 2022

Page: [200 - 210] Pages: 11

DOI: 10.2174/1574892817666220510123820

Price: $65

Abstract

Background: Tumor metastasis is a main cause of death in patients with breast cancer. The cross-talk between cancer-associated fibroblasts (CAFs) and tumor cells plays an important role in promoting tumor invasion and metastasis. It is important to develop a novel delivery system to inhibit tumor development by simultaneously targeting both CAFs and tumor cells.

Objectives: The main objective of this research was to prepare nanoparticles to inhibit tumor proliferation and migration by blocking the cross-talk of tumor-CAFs. Additionally, a novel “MCF- 7+NIH/3T3” mixed cell model was established to mimic the tumor microenvironment (TME).

Methods: In this study, the pH-responsive nanoparticles (MIF/DOX-sul-HA NPs) based on sulfated hyaluronic acid (sul-HA) polymers were prepared for co-delivery of doxorubicin (DOX) and mifepristone (MIF). The effects of anti-proliferation and anti-metastasis of MIF/DOX-sul-HA NPs were investigated both in vitro and in vivo.

Results: The results showed that MIF/DOX-sul-HA NPs were nearly spherical in shape with narrow particle size distribution and pH-responsive drug release, and could be taken up by both MCF-7 and NIH/3T3 cells. Compared with MCF-7 cells alone, the anti-tumor effect of single DOX was weak in the “MCF-7+NIH/3T3” mixed cell model. MIF/DOX-sul-HA NPs exhibited strong effects of anti-proliferation and anti-metastasis than the free single drug.

Conclusion: The sul-HA nanoparticles for co-delivery of DOX and MIF could be a promising combined therapy strategy for the treatment of breast cancer.

Keywords: Breast cancer, delivery, nanoparticles, combination, fibroblast, CAFs.

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