Injectable Doxorubicin-loaded Hyaluronic Acid-based Hydrogel for Locoregional Therapy and Inhibiting Metastasis of Breast Cancer

Abstract

Therapy and metastasis pose significant challenges for breast cancer therapy. Locoregional chemotherapy presents a promising strategy to address these dilemmas. In this study, a doxorubicin-loaded injectable hydrogel based on hyaluronic acid (DOX-MCHAgel) was fabricated for locoregional chemotherapy and inhibiting the metastasis of breast cancer. The high bio-safety of cargo-free hydrogels (MCHAgel) would enhance patient compliance. The sustained DOX release behaviors from DOX-MCHAgel (over 10 days) could reduce dosing frequency and achieve long-term therapeutic effects. The potent in vivo anti-tumor activity of DOX-MCHAgel was verified by the smallest tumor volumes, the largest number of apoptotic cells, and the strongest fluorescence intensity in TUNEL staining. Notably, the injectable DOX-MCHAgel not only greatly suppressed the growth of 4T1 tumor tissues, but also effectively curbed the liver and lung metastasis in vivo. Moreover, the survival of 4T1-tumor bearing mice was extended without obvious systemic toxicity. In brief, the novel injectable hydrogel developed in this study offers a new strategy for locoregional therapy and inhibiting metastasis of breast cancer.