Multifunctional hydrogel for synergistic reoxygenation and chemo/photothermal therapy in metastatic breast cancer recurrence and wound infection

• Published in: Journal of controlled release Vol. 365; pp. 74 - 88
• Main Authors: Chen, Jing, Zhang, Xinyi, Zhang, Jinshen, Wang, Zhaoxia, Zhu, Guilan, Geng, Ming, Zhu, Jinmiao, Chen, Yajun, Wang, Wei, Xu, Youcui
• Format: Journal Article
• Language: English
• Published: Netherlands 01.01.2024
• Subjects: Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; Cell Line, Tumor; Doxorubicin; Female; Humans; Hydrogels - chemistry; Hyperthermia, Induced - methods; Phototherapy - methods; Photothermal Therapy; Surgical Wound Infection - therapy; Tumor Microenvironment; Metastatic breast cancer; Multifunctional responsive hydrogels; Infected-wound healing; ROS scavenging; Chemo/photothermal therapy
• ISSN: 0168-3659; 1873-4995; 1873-4995
• DOI: 10.1016/j.jconrel.2023.11.024

Metastatic recurrence and postoperative wound infection are two major challenges for breast cancer patients. In this study, a multifunctional responsive hydrogel system was developed for synergistic reoxygenation and chemo/photothermal therapy in metastatic breast cancer and wound infection. The hydrogel system was obtained by cross-linking Prussian blue-modified N-carboxyethyl chitosan (PBCEC) and oxidized sodium alginate using the amino and aldehyde groups on the polysaccharides, resulting in the formation of responsive dynamic imine bonds. Conditioned stimulation (e.g., acid microenvironment) enabled the controlled swelling of hydrogels as well as subsequent slow release of loaded doxorubicin (DOX). Additionally, this hydrogel system decomposed endogenous reactive oxygen species into oxygen to relieve the hypoxic tumor microenvironment and promote the healing of infected-wounds. Both in vitro and in vivo experiments demonstrated the synergistic reoxygenation and chemo/photothermal effects of the PB/DOX hydrogel system against metastatic breast cancer and its recurrence, as well as postoperative wound infection. Thus, the combination of reoxygenation and chemo/photothermal therapy represents a novel strategy for treating and preventing tumor recurrence and associated wound infection.