He Jiao, Li Jiayu, Li Min, He Zhidi, Ye Yunxia, Li Jiaxin, Rao Jingdong, Zhao Xin, Li Man, He Qin
Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, Sichuan University, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
Department of Applied Biology and Chemical Technology, the Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong SAR, China.
Nanoscale. 2025 Jan 16;17(3):1510-1523. doi: 10.1039/d4nr02757d.
Bacterial outer membrane vesicles (OMVs), produced by Gram-negative bacteria, retain the immunostimulatory capacity of parental bacteria. OMVs have been recognized as potent natural immune adjuvants and drug delivery vehicles. Photothermal therapy that triggers immunogenic cell death further stimulates the immune system by releasing damage-associated molecular patterns. This therapeutic effect can be synergized with OMVs to achieve enhanced anti-tumor outcomes. We also observed that tumors can recruit platelets. Leveraging the phenomenon, we have innovatively employed platelets as "couriers" to boost the tumor-targeting delivery efficiency of both OMVs and photothermal agents. In detail, based on OMVs, we meticulously engineered nanoparticles (IR780-SLN@O-P) with platelet-binding capacity. These "courier" platelets carry "cargo" IR780-SLN@O-P NPs to tumor sites P-selectin, ensuring targeted delivery. Under laser irradiation, the photothermal agents generate significant photothermal effects, which combined with the immune-stimulating properties of OMVs, creating a robust anti-tumor immune response. For "cold" tumors such as triple-negative breast cancer (TNBC), our IR780-SLN@O-P NPs not only prolonged the survival of mice bearing 4T1 orthotopic tumors, but also significantly suppressed tumor growth. Moreover, they facilitated dendritic cell maturation and the infiltration of CD8 T cells to ameliorate the immunosuppressive tumor environment. Our research aims to highlight the unique advantages of OMVs and explore the potential of the tumor-targeting strategy that synergizes photothermal therapy with immunotherapy. We hope that our findings can offer insights into TNBC clinical treatments.
革兰氏阴性菌产生的细菌外膜囊泡（OMV）保留了亲本细菌的免疫刺激能力。OMV已被公认为是有效的天然免疫佐剂和药物递送载体。触发免疫原性细胞死亡的光热疗法通过释放损伤相关分子模式进一步刺激免疫系统。这种治疗效果可以与OMV协同作用，以实现增强的抗肿瘤效果。我们还观察到肿瘤可以募集血小板。利用这一现象，我们创新性地利用血小板作为“信使”，以提高OMV和光热剂的肿瘤靶向递送效率。具体而言，基于OMV，我们精心设计了具有血小板结合能力的纳米颗粒（IR780-SLN@O-P）。这些“信使”血小板将“货物”IR780-SLN@O-P纳米颗粒携带到肿瘤部位，通过P-选择素确保靶向递送。在激光照射下，光热剂产生显著的光热效应，与OMV的免疫刺激特性相结合，产生强大的抗肿瘤免疫反应。对于三阴性乳腺癌（TNBC）等“冷”肿瘤，我们的IR780-SLN@O-P纳米颗粒不仅延长了携带4T1原位肿瘤小鼠的生存期，还显著抑制了肿瘤生长。此外，它们促进了树突状细胞成熟和CD8 T细胞浸润，以改善免疫抑制性肿瘤环境。我们的研究旨在突出OMV的独特优势，并探索将光热疗法与免疫疗法协同作用的肿瘤靶向策略的潜力。我们希望我们的发现能够为TNBC临床治疗提供见解。
