文献类型：期刊文献

英文题名：Construction of In Situ Personalized Cancer Vaccines by Bioorthogonal Catalytic Microneedles for Augmented Melanoma Immunotherapy

作者：Xu, Qian-He[1];Yin, Xiu-Yuan[1];Chen, Zhen-Qiang[1];Huang, En-Kui[1];Yao, Xiaojun[2];Li, Xingguang[1];Liu, Pei-Nian[1,3]

机构：[1]East China Univ Sci & Technol, Sch Chem & Mol Engn, Shanghai Key Lab Funct Mat Chem, Key Lab Adv Mat, Shanghai 200237, Peoples R China;[2]Macao Polytech Univ, Fac Appl Sci, Ctr Artificial Intelligence Driven Drug Discovery, Macau 999078, Peoples R China;[3]China Pharmaceut Univ, Sch Pharm, State Key Lab Nat Med, Nanjing 211198, Peoples R China

年份：2025

卷号：21

期号：18

外文期刊名：SMALL

收录：;EI(收录号：20251318128702);WOS:【SCI-EXPANDED(收录号:WOS:001451492200001)】；

基金：This work was supported by the National Natural Science Foundation of China (Nos. 22201073, 22161160319, and 21925201) and the Macao Science and Technology Development Fund (0030/2024/RIA1). The author thanks the Research Center of Analysis and Testing of East China University of Science and Technology for help in the characterization.

语种：英文

外文关键词：bioorthogonal catalysis; cancer immunotherapy; cancer vaccines; immunogenic cell death; microneedle

摘要：In situ personalized tumor vaccines are produced directly at the primary tumor site by killing cancer cells and stimulating immune cells, they are effective against individuals and bypass the complexity and high cost of in vitro vaccine production. However, their clinical application is hindered by insufficient efficiency in inducing immunogenic cancer cell death (ICD) and systemic inflammation caused by immune adjuvants. Here, personalized cancer vaccines are constructed in situ for melanoma immunotherapy based on bioorthogonal catalytic microneedles, which enable the catalytic release of prodrugs at tumor sites and mediate strong ICD and an enhanced tumor immune response while avoiding systemic immune storms and toxic side effects. By incorporating TiO2 nanosheets supported Pd into swellable microneedles, the bioorthogonal microneedles are constructed to catalyze the depropargylation reaction of doxorubicin (DOX) prodrug and imiquimod (IMQ) prodrug in situ. The activated DOX at subcutaneous tumor sites induced strong ICD and released tumor-associated antigens. Concurrently, the activated IMQ acts as a Toll-like receptor (TLR7) agonist, enhancing the anti-tumor immune response. In vivo experiments demonstrate that this immunotherapy achieves approximate to 97% inhibition of primary tumors and effectively inhibits untreated distant tumors (approximate to 94% inhibition) and lung metastasis (approximate to 92% inhibition).