文献类型：期刊文献

英文题名：Research advances in immune agonists and their nanoparticles for enhancing the immunotherapeutic efficacy of PD-1 inhibitors in malignancies

作者：Xia, Renjie[1,2];Liang, Juan[3];Ma, Jianguo[2,4];Du, Xiaoyu[1,2];Ma, Liangbin[1,2];Han, Xiongxiong[2,4];Wang, Yong[2,4];Qin, Jianwei[2];Yan, Long[2]

第一作者：Xia, Renjie

通信作者：Qin, JW[1];Yan, L[1]

机构：[1]Northwest Minzu Univ, Dept Med, Lanzhou, Peoples R China;[2]940th Hosp Joint Logist Support Force Chinese Peop, Dept Hepatobiliary Surg, Lanzhou, Peoples R China;[3]940th Hosp Joint Logist Support Force Chinese Peop, Intens Care Units, Lanzhou, Peoples R China;[4]Gansu Univ Chinese Med, Sch Clin Med 1, Lanzhou, Peoples R China

第一机构：Northwest Minzu Univ, Dept Med, Lanzhou, Peoples R China

通信机构：[1]corresponding author), 940th Hosp Joint Logist Support Force Chinese Peop, Dept Hepatobiliary Surg, Lanzhou, Peoples R China.

年份：2025

卷号：15

外文期刊名：FRONTIERS IN ONCOLOGY

收录：;Scopus(收录号：2-s2.0-105015332477);WOS:【SCI-EXPANDED(收录号:WOS:001566249000001)】；

基金：The author(s) declare financial support was received for the research and/or publication of this article. This work was supported by the Gansu Provincial Natural Science Foundation (22JR5RA008), the Science and Technology Program of Lanzhou City (2024-9-152), and the Science and Technology Program of Lanzhou City (2024-9-131).

语种：英文

外文关键词：immune agonists; PD-1 inhibitors; nanoparticle delivery systems; tumor immunotherapy; combinatorial therapy; immunotoxicity

摘要：Immune checkpoint blockade (ICB), particularly targeting programmed cell death-1 (PD-1), has revolutionized cancer immunotherapy but remains limited by heterogeneous therapeutic responses and immune-related toxicities. This review systematically examines the integration of immune agonists-STING, TLR, CD40, and OX40 agonists-with PD-1 inhibitors to overcome resistance and amplify antitumor immunity. Nanoparticle delivery systems emerge as transformative platforms, addressing critical limitations of free agonists, including enzymatic degradation, off-target toxicity, and poor pharmacokinetics. By leveraging tunable physicochemical properties (e.g., size, surface charge, stimuli-responsive release), nanoparticles enhance tumor-specific accumulation, prolong agonist half-life, and synergize with PD-1 inhibitors to remodel immunosuppressive microenvironments. Preclinical and early clinical studies demonstrate combinatorial strategies achieving increases in T cell infiltration and enhancements in anti-angiogenic activity compared to monotherapies. However, translational challenges persist, including nanoparticle-induced immunotoxicity (ROS-mediated inflammation), manufacturing scalability hurdles, and interspecies discrepancies in murine models. Future directions emphasize personalized nanovaccines, supramolecular cytosolic delivery systems (e.g., Calix-STING), and biomarker-driven trials to optimize efficacy in advanced pancreatic, melanoma, and immunologically quiescent tumors. This work underscores the imperative for interdisciplinary collaboration to standardize nanoparticle design and clinical validation frameworks, ultimately bridging the gap between nanomedicine innovation and oncology practice.