Yu Zhaolong, Gan Ziqi, Wu Wei, Sun Xiaojiang, Cheng Xiaofei, Chen Chen, Cao Bihui, Sun Zhongyi, Tian Jiwei
Shanghai Key Laboratory of Orthopaedic Implant, Department of Orthopaedics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.
Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou 510055, China.
ACS Appl Mater Interfaces. 2024 Dec 11;16(49):67225-67234. doi: 10.1021/acsami.4c12532. Epub 2024 Nov 26.
Osteosarcoma, a predominant malignant tumor among adolescents, exhibits high mortality and suboptimal immunotherapy efficacy due to a collagen-dense extracellular matrix (ECM) that hinders cytotoxic T lymphocyte (CTL) infiltration. Herein, we developed mesoporous polydopamine (MPDA) nanoparticles encapsulating bromelain and the immune adjuvant R848 (M@B/R), aimed at enhancing photothermal immunotherapy. These nanoparticles efficiently accumulate at the tumor site following injection. Upon near-infrared (NIR) light irradiation, photothermal therapy (PTT) induces immunogenic cell death in tumor cells and, with the aid of R848, efficiently promotes dendritic cell maturation, activating antitumor immunity and leading to CTL infiltration into the tumor. Concurrently, NIR-induced heating activates bromelain, resulting in ECM degradation and improved CTL penetration into the tumor. Our evaluations demonstrate potent antitumor effects in osteosarcoma-bearing mice. This integrated approach offers a promising strategy for overcoming physical barriers in ECM-rich tumors, marking a significant advancement in the treatment of osteosarcoma.
骨肉瘤是青少年中主要的恶性肿瘤，由于其富含胶原蛋白的细胞外基质（ECM）阻碍细胞毒性T淋巴细胞（CTL）浸润，导致死亡率高且免疫治疗效果欠佳。在此，我们开发了包裹菠萝蛋白酶和免疫佐剂R848（M@B/R）的介孔聚多巴胺（MPDA）纳米颗粒，旨在增强光热免疫治疗。注射后，这些纳米颗粒能有效积聚在肿瘤部位。在近红外（NIR）光照射下，光热疗法（PTT）诱导肿瘤细胞发生免疫原性细胞死亡，并在R848的帮助下，有效促进树突状细胞成熟，激活抗肿瘤免疫，导致CTL浸润到肿瘤中。同时，近红外诱导的加热激活菠萝蛋白酶，导致ECM降解，并改善CTL向肿瘤内的渗透。我们的评估证明了其对荷骨肉瘤小鼠具有强大的抗肿瘤作用。这种综合方法为克服富含ECM的肿瘤中的物理屏障提供了一种有前景的策略，标志着骨肉瘤治疗取得了重大进展。
