In situ injectable hydrogel encapsulating Mn/NO-based immune nano-activator for prevention of postoperative tumor recurrence

作     者：Shengnan Huang Chenyang Zhou Chengzhi Song Xiali Zhu Mingsan Miao Chunming Li Shaofeng Duan Yurong Hu Shengnan Huang;Chenyang Zhou;Chengzhi Song;Xiali Zhu;Mingsan Miao;Chunming Li;Shaofeng Duan;Yurong Hu

作者机构：Academy of Chinese Medical SciencesHenan University of Chinese MedicineZhengzhou 450046China School of Pharmaceutical SciencesHenan Key Laboratory of Targeting Therapy and Diagnosis for Critical DiseasesZhengzhou UniversityZhengzhou 450001China Center for Quantitative BiologyPeking UniversityBeijing 100871China School of Pharmaceutical SciencesHenan University of Chinese MedicineZhengzhou 450046China Department of PharmacyChongqing University Cancer HospitalChongqing 400030China School of Pharmaceutical SciencesHenan UniversityZhengzhou 450046China 

出 版 物：《Asian Journal of Pharmaceutical Sciences》 (亚洲药物制剂科学（英文）)

年 卷 期：2024年第19卷第2期

页      面：102-119页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：supported by the National Natural Science Foundation of China(No.82003298) the Scientiffc and Technological Project of Henan Province(No.232102310392) the Key Research and Development Projects of Henan Province(No.222102310453,212102311025) Postdoctoral Research Grant in Henan Province(No.201901025) the Key Research Project of Henan Higher Education Institutions(No.18A350003) Open Fund of Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases,Henan Province(No.NMZL2020102) the Natural Science Foundation of Chongqing(No.cstc2019jcyj-msxmX0035) the Scientiffc Research Seedling Project of Chongqing Medicinal Biotechnology Association(No.cmba2022kyym-zkxmQ0009) 

主　　题：Post-sur gical tumor recurrence In situl hydrogel Immunotherapy Tumor micr oenvir onment Manganese(Ⅱ) Nitic oxide 

摘      要：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.