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

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.

• Authors: Di Wang, Jingliang Wu, Cuiping Qi, Jinping Dong, Xueying Ding, Guohua Yu, Shuzhen Liu, Bo Zhang, Zhiqin Gao, Xiuhong Wei, Hongying Liu
• Journal: Recent patents on anti-cancer drug discovery (Recent Pat Anticancer Drug Discov) Vol. 18 Issue 2 Pg. 200-210 ( 2022) ISSN: 2212-3970 [Electronic] United Arab Emirates
• PMID: 35538821 (Publication Type: Journal Article)
• Copyright: Copyright© Bentham Science Publishers; For any queries, please email at [email protected].

Chemical References

• Hyaluronic Acid
• Sulfates
• Doxorubicin

Topics

• Mice
• Animals
• Humans
• Female
• Breast Neoplasms (drug therapy)
• Hyaluronic Acid (pharmacology, therapeutic use)
• Sulfates (therapeutic use)
• Cancer-Associated Fibroblasts
• Doxorubicin (pharmacology, therapeutic use)
• Nanoparticles
• MCF-7 Cells
• Hydrogen-Ion Concentration
• Drug Delivery Systems (methods)
• Tumor Microenvironment