Yan Feng, Jing Chengwei, Duan Shao, Xia Yifei, Xiao Runzhu, Shao Shuaiming, Xiao Zunyu, Chen Weiyu, Li Chao
Department of Orthopedics, The People's Hospital of Suzhou New District, Suzhou 215000, China.
Department of Nuclear Medicine, The First Affiliated Hospital of Ningbo University, Ningbo 315100, China.
ACS Biomater Sci Eng. 2025 Aug 11;11(8):4931-4940. doi: 10.1021/acsbiomaterials.5c00333. Epub 2025 Jul 13.
Osteosarcoma is a malignant bone tumor that is extremely aggressive and presents several therapeutic problems. Although CD40 agonist antibodies (αCD40) have demonstrated potential in improving T cell priming and reprogramming tumor-associated macrophages, osteosarcoma's poor immunogenicity leads to "cold" tumors that are challenging to cure. When it comes to triggering immunological responses, the STING pathway is essential. To further improve this impact, cGAMP was stabilized and delivered using layered double hydroxide (LDH) nanoparticles cross-linked with bovine serum albumin (BSA). BSA-LDHs-cGAMP improved the infiltration of CD40+ macrophages and DC cells, which, in turn, improved the therapeutic impact of αCD40 immunotherapy. These results offer a promising in situ cancer treatment and show the possibility of αCD40 boosters in bone tumor therapy.
骨肉瘤是一种极具侵袭性的恶性骨肿瘤，存在诸多治疗难题。尽管CD40激动剂抗体（αCD40）已显示出在改善T细胞启动和重编程肿瘤相关巨噬细胞方面的潜力，但骨肉瘤较差的免疫原性导致其成为难以治愈的“冷”肿瘤。在触发免疫反应方面，STING通路至关重要。为进一步增强这种效果，使用与牛血清白蛋白（BSA）交联的层状双氢氧化物（LDH）纳米颗粒来稳定和递送环状二核苷酸单磷酸腺苷（cGAMP）。BSA-LDHs-cGAMP改善了CD40+巨噬细胞和树突状细胞（DC细胞）的浸润，进而提高了αCD40免疫疗法的治疗效果。这些结果为原位癌症治疗提供了有前景的方案，并显示了αCD40增强剂在骨肿瘤治疗中的可能性。
