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Environment-responsive dendrobium polysaccharide hydrogel embedding manganese microsphere as a post-operative adjuvant to boost cascaded immune cycle against melanoma

文献类型：期刊论文

作者Gao, Nan6,7; Huang, Yiran6,7; Jing, Shisuo6; Zhang, Meng5; Liu, Ergang6; Qiu, Lu4,6; Huang, Jing7; Muhitdinov, Bahtiyor3; Huang, Yongzhuo1,2,6,7
刊名THERANOSTICS
出版日期2024
卷号14期号:10页码:3810-3826
关键词post-operative implantation dendrobium hydrogel manganese pectin microspheres cancer metalloimmunotherapy tumor recurrence metastasis
ISSN号1838-7640
DOI10.7150/thno.94354
通讯作者Liu, Ergang(liuergang@zidd.ac.cn) ; Huang, Yongzhuo(yzhuang@simm.ac.cn)
英文摘要Rationale: Surgical resection is a primary treatment for solid tumors, but high rates of tumor recurrence and metastasis post-surgery present significant challenges. Manganese (Mn 2+ ), known to enhance dendritic cell-mediated cancer immunotherapy by activating the cGAS-STING pathway, has potential in post-operative cancer management. However, achieving prolonged and localized delivery of Mn 2+ to stimulate immune responses without systemic toxicity remains a challenge. Methods: We developed a post-operative microenvironment-responsive dendrobium polysaccharide hydrogel embedded with Mn 2+-pectin microspheres (MnP@DOP-Gel). This hydrogel system releases Mn 2+-pectin microspheres (MnP) in response to ROS, and MnP shows a dual effect in vitro : promoting immunogenic cell death and activating immune cells (dendritic cells and macrophages). The efficacy of MnP@DOP-Gel as a post-surgical treatment and its potential for immune activation were assessed in both subcutaneous and metastatic melanoma models in mice, exploring its synergistic effect with anti-PD1 antibody. Result: MnP@DOP-Gel exhibited ROS-responsive release of MnP, which could exert dual effects by inducing immunogenic cell death of tumor cells and activating dendritic cells and macrophages to initiate a cascade of anti-tumor immune responses. In vivo experiments showed that the implanted MnP@DOP-Gel significantly inhibited residual tumor growth and metastasis. Moreover, the combination of MnP@DOP-Gel and anti-PD1 antibody displayed superior therapeutic potency in preventing either metastasis or abscopal brain tumor growth. Conclusions: MnP@DOP-Gel represents a promising drug-free strategy for cancer post-operative management. Utilizing this Mn 2+-embedding and ROS-responsive delivery system, it regulates surgery-induced immune responses and promotes sustained anti-tumor responses, potentially increasing the effectiveness of surgical cancer treatments.
WOS关键词CANCER-SURGERY
资助项目National Key Research and Development Program of China (China)[2021YFE0103100] ; National Key Research and Development Program of China (China)[2022YFE0203600] ; National Key Research and Development Program of China (China)[2021YFC2400600] ; NSFC[81925035] ; NSFC[82341232] ; Department of Science and Technology of Guangdong Province (High-level new RD institute)[2019B090904008] ; Chinese Academy of Sciences President's International Fellowship Initiative[2024VBB0004] ; SciTech Innovation Leading Talent Projects in Zhongshan[LJ2021001] ; Scientific Innovation Group Project in Zhongshan[CXTD2022011] ; Department of Science and Technology of Guangdong Province (High-level Innovative Research Institute)[2021B0909050003]
WOS研究方向Research & Experimental Medicine
语种英语
WOS记录号WOS:001266358900003
出版者IVYSPRING INT PUBL
源URL[http://119.78.100.183/handle/2S10ELR8/312273]  
专题中国科学院上海药物研究所
通讯作者Liu, Ergang; Huang, Yongzhuo
作者单位1.NMPA Key Lab Qual Res & Evaluat Pharmaceut Excipie, Shanghai 201203, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
3.Uzbek Acad Sci, Inst Bioorgan Chem, Tashkent 100125, Uzbekistan
4.Guangzhou Univ Chinese Med, Artemisinin Res Ctr, Guangzhou 510450, Peoples R China
5.Zhejiang Univ, Womens Hosp, Dept Pharm, Sch Med, Hangzhou 310006, Peoples R China
6.Chinese Acad Sci, Zhongshan Inst Drug Discovery, SIMM, Zhongshan 528400, Peoples R China
7.Guizhou Med Univ, Sch Pharm, Guiyang 561113, Guizhou, Peoples R China
推荐引用方式
GB/T 7714		 Gao, Nan,Huang, Yiran,Jing, Shisuo,et al. Environment-responsive dendrobium polysaccharide hydrogel embedding manganese microsphere as a post-operative adjuvant to boost cascaded immune cycle against melanoma[J]. THERANOSTICS,2024,14(10):3810-3826.
APA Gao, Nan.,Huang, Yiran.,Jing, Shisuo.,Zhang, Meng.,Liu, Ergang.,...&Huang, Yongzhuo.(2024).Environment-responsive dendrobium polysaccharide hydrogel embedding manganese microsphere as a post-operative adjuvant to boost cascaded immune cycle against melanoma.THERANOSTICS,14(10),3810-3826.
MLA Gao, Nan,et al."Environment-responsive dendrobium polysaccharide hydrogel embedding manganese microsphere as a post-operative adjuvant to boost cascaded immune cycle against melanoma".THERANOSTICS 14.10(2024):3810-3826.

入库方式： OAI收割

来源：上海药物研究所

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