An immunotherapeutic hydrogel booster inhibits tumor recurrence and promotes wound healing for postoperative management of melanoma  

作　　者：Yuanyuan Yang Bo Zhang Yangtao Xu Wenxiang Zhu Zinian Zhu Xibo Zhang Wenze Wu Jierong Chen Zhiqiang Yu 

机构地区：[1]Department of Laboratory Medicine,Dongguan Institute of Clinical Cancer Research,Dongguan Key Laboratory of Precision Diagnosis and Treatment for Tumors,The Tenth Affiliated Hospital of Southern Medical University(Dongguan People’s Hospital),Dongguan,523058,China [2]Jingzhou Central Hospital,Jingzhou Hospital Affiliated to Yangtze University,Jingzhou,434020,China [3]Institute of Biomedical Health Technology and Engineering,Shenzhen Bay Laboratory,Shenzhen,518132,China [4]Laboratory Medicine,Guangdong Provincial People’s Hospital,Guangdong Academy of Medical Sciences,Guangzhou,510080,China

出　　处：《Bioactive Materials》2024年第12期178-193,共16页生物活性材料（英文）

基　　金：supported by the National Natural Science Foundation of China(82372115 and 52073139);the China Postdoctoral Science Foundation(2023M731571);Dongguan Science and Technology of Social Development Program(20231800900322 and 20231800900362);the Postdoctoral Research Project Start-Up Funding of Dongguan People’s Hospital(319341);the Guangdong Basic and Applied Basic Research Foundation(2023B1515120084 and 2023A1515110016);the Training Program of National Natural Science Foundation of Dongguan People’s Hospital(Z202402).

摘　　要：Low tumor immunogenicity,immunosuppressive tumor microenvironment,and bacterial infections have emerged as significant challenges in postsurgical immunotherapy and skin regeneration for preventing melanoma recurrence.Herein,an immunotherapeutic hydrogel booster(GelMA-CJCNPs)was developed to prevent postoperative tumor recurrence and promote wound healing by incorporating ternary carrier-free nanoparticles(CJCNPs)containing chlorine e6(Ce6),a BRD4 inhibitor(JQ1),and a glutaminase inhibitor(C968)into methacrylic anhydride-modified gelatin(GelMA)dressings.GelMA-CJCNPs reduced glutathione production by inhibiting glutamine metabolism,thereby preventing the destruction of reactive oxygen species generated by photodynamic therapy,which could amplify oxidative stress to induce severe cell death and enhance immunogenic cell death.In addition,GelMA-CJCNPs reduced M2-type tumor-associated macrophage polarization by blocking glutamine metabolism to reverse the immunosuppressive tumor microenvironment,recruiting more tumor-infiltrating T lymphocytes.GelMA-CJCNPs also downregulated IFN-γ-induced expression of programmed cell death ligand 1 to mitigate acquired immune resistance.Benefiting from the amplified systemic antitumor immunity,GelMA-CJCNPs markedly inhibited the growth of both primary and distant tumors.Moreover,GelMA-CJCNPs demonstrated satisfactory photodynamic antibacterial effects against Staphylococcus aureus infections,thereby promoting postsurgical wound healing.Hence,this immunotherapeutic hydrogel booster,as a facile and effective postoperative adjuvant,possesses a promising potential for inhibiting tumor recurrence and accelerating skin regeneration.

关 键 词：Glutamine metabolism IMMUNOTHERAPY HYDROGEL MELANOMA Wound healing 

分 类 号：TQ427.26[化学工程] R730.51[医药卫生—肿瘤]