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- Title
In situ injectable hydrogel encapsulating Mn/NO-based immune nano-activator for prevention of postoperative tumor recurrence.
- Authors
Shengnan Huang; Chenyang Zhou; Chengzhi Song; Xiali Zhu; Mingsan Miao; Chunming Li; Shaofeng Duan; Yurong Hu
- Abstract
Postoperative tumor recurrence remains a predominant cause of treatment failure. In this study, we developed an in situ injectable hydrogel, termed MPB-NO@DOX + ATRA gel, which was locally formed within the tumor resection cavity. The MPB-NO@DOX + ATRA gel was fabricated by mixing a thrombin solution, a fibrinogen solution containing all-trans retinoic acid (ATRA), and a Mn/NO-based immune nano-activator termed MPB-NO@DOX. ATRA promoted the differentiation of cancer stem cells, inhibited cancer cell migration, and affected the polarization of tumor-associated macrophages. The outer MnO2 shell disintegrated due to its reaction with glutathione and hydrogen peroxide in the cytoplasm to release Mn2+ and produce O2, resulting in the release of doxorubicin (DOX). The released DOX entered the nucleus and destroyed DNA, and the fragmented DNA cooperated with Mn2+ to activate the cGAS-STING pathway and stimulate an anti-tumor immune response. In addition, when MPB-NO@DOX was exposed to 808 nm laser irradiation, the Fe-NO bond was broken to release NO, which downregulated the expression of PD-L1 on the surface of tumor cells and reversed the immunosuppressive tumor microenvironment. In conclusion, the MPB-NO@DOX + ATRA gel exhibited excellent anti-tumor efficacy. The results of this study demonstrated the great potential of in situ injectable hydrogels in preventing postoperative tumor recurrence.
- Subjects
DISEASE relapse; CANCER cell differentiation; CANCER cell migration; CANCER stem cells; TUMOR microenvironment
- Publication
Asian Journal of Pharmaceutical Sciences, 2024, Vol 19, Issue 2, p1
- ISSN
1818-0876
- Publication type
Article
- DOI
10.1016/j.ajps.2024.100901