肝细胞癌（HCC）免疫治疗的临床疗效因肿瘤的低免疫原性而受到显着限制。最近的研究表明焦亡和光热疗法都可以有效诱导肝癌细胞中的肿瘤免疫原性细胞死亡（ICD）。重楼的主要活性成分重楼素II（PPII）首次被证明可以诱导肿瘤细胞焦亡，而IR780则被808 nm激光激活，将光能转化为热能，有效消灭肿瘤细胞。然而，PPII和IR780都面临着溶解度低、靶向性差等挑战，极大地限制了它们的应用。针对这些问题，通过沉淀法将焦亡诱导剂PPII和光敏剂IR780共负载到PLGA纳米颗粒中，并在纳米颗粒表面修饰适配体AS1411，构建靶向纳米颗粒（Apt/PPII/IR780-NPs）。该纳米颗粒具有pH/NIR双响应智能释放特性，实现了药物在肿瘤部位的靶向控释。此外，它在激光照射下可以快速释放PPII诱导细胞焦亡，与基于IR780的光热疗法相结合，在体外和体内发挥显着的协同抗肿瘤作用。这一过程不仅促进DC成熟并激活效应T细胞，从而启动适应性免疫，而且产生持久有效的免疫记忆。此外，Apt/PPII/IR780-NPs 显着提高了 Anti-PD-1 功效。总之，基于 Apt/PPII/IR780-NPs 的化学光热疗法可以显着增强肿瘤 ICD，这为 HCC 免疫治疗提供了一种有前景的新策略。© 2024。作者。

The clinical efficacy of immunotherapy for hepatocellular carcinoma (HCC) is significantly limited by the low immunogenicity of the tumor. Recent studies have revealed that both pyroptosis and photothermal therapy can effectively induce tumor immunogenic cell death (ICD) in liver cancer cells. Polyphyllin II (PPII), the major active component of Rhizoma Paridis, has been demonstrated for the first time to induce pyroptosis in tumor cells, while IR780 is activated by 808 nm laser to transform light energy into heat energy, effectively eliminating tumor cells. However, both PPII and IR780 are afflicted with challenges such as low solubility and poor targeting, significantly limiting their utilization. To address these problems, the pyroptosis inducer PPII and photosensitizer IR780 were co-loaded in PLGA nanoparticles by precipitation method, and the aptamer AS1411 was modified on the surface of nanoparticles to construct the targeting nanoparticles (Apt/PPII/IR780-NPs). The nanoparticles exhibit a pH/NIR dual-response intelligent release feature, which realizes the targeted and controlled release of drugs in tumor site. Furthermore, it can rapidly release PPII to induce cell pyroptosis under laser irradiation, combining with IR780-based photothermal therapy exert a significant synergistic anti-tumor effect in vitro and in vivo. This process not only promotes maturation of DCs and activates effector T cells, thereby initiating adaptive immunity, but also generates enduring and effective immune memory. In addition, Apt/PPII/IR780-NPs significantly improved the Anti-PD-1 efficacy. In summary, chemo-photothermal therapy based on Apt/PPII/IR780-NPs can significantly enhance tumor ICD, which provides a promising new strategy for HCC immunotherapy.© 2024. The Author(s).