School of pharmaceutical sciences, Capital medical university, Beijing 100069, PR China.
School of pharmaceutical sciences, Capital medical university, Beijing 100069, PR China.
Biomater Adv. 2024 Nov;164:213996. doi: 10.1016/j.bioadv.2024.213996. Epub 2024 Aug 10.
Therapeutic vaccine becomes a promising strategy to fight cancer by enhancing and sustaining specific anti-tumor immune responses. However, its efficacy is often impeded by low immunogenicity, the immunosuppressive tumor microenvironment (TME), and immune-related adverse events. Herein, we introduce 1-tetradecanol (TD)-wrapped, CpG-loaded porous Prussian blue nanoparticles (pPBNPs-CpG@TD) as a nanoimmunomodulator to initiate photothermal-induced immunogenic cell death (ICD) and photothermal-responsive release of CpG for augmenting the ICD effect. It was revealed that the dual-photothermal action significantly potentiated the in situ anti-tumor vaccine-like immunotherapy in terms of enhanced immunogenicity, promoted dendritic cell maturation, and increased T lymphocyte infiltration, consequently eliciting a robust immune response for inhibiting both primary and rechallenge tumors on a subcutaneous 4T1 tumor-bearing mouse model. The development and use of photoactive nanoimmunomodulators represents a novel and effective strategy to boost immunogenicity and counteract immunosuppressive TME, marking a significant advancement in the realm of ICD-driven in situ anti-tumor vaccine-like immunotherapy.
治疗性疫苗通过增强和维持特异性抗肿瘤免疫反应成为一种有前途的抗癌策略。然而，其疗效常受到免疫原性低、免疫抑制性肿瘤微环境（TME）和免疫相关不良事件的阻碍。在此，我们介绍了 1-十四醇（TD）包裹的、载 CpG 的多孔普鲁士蓝纳米粒子（pPBNPs-CpG@TD）作为一种纳米免疫调节剂，以引发光热诱导的免疫原性细胞死亡（ICD）和 CpG 的光热响应释放，从而增强 ICD 效应。结果表明，双重光热作用显著增强了原位抗肿瘤疫苗样免疫治疗的效果，增强了免疫原性，促进了树突状细胞成熟，增加了 T 淋巴细胞浸润，从而在皮下 4T1 荷瘤小鼠模型上引发了强烈的免疫反应，抑制了原发性和再挑战肿瘤。光活性纳米免疫调节剂的开发和应用代表了一种增强免疫原性和对抗免疫抑制性 TME 的新策略，标志着 ICD 驱动的原位抗肿瘤疫苗样免疫治疗领域的重大进展。
