多晶林II和IR780 PLGA纳米颗粒的共传递与光热结合，以增强肝细胞癌免疫疗法
Co-delivery of polyphyllin II and IR780 PLGA nanoparticles induced pyroptosis combined with photothermal to enhance hepatocellular carcinoma immunotherapy
影响因子:12.60000
分区:生物学1区 Top / 生物工程与应用微生物1区 纳米科技2区
发表日期:2024 Oct 21
作者:
Huating Huang, Jing Fu, Hulinyue Peng, Yuanyuan He, Aqian Chang, Huizhong Zhang, Yang Hao, Xiaohan Xu, Shiman Li, Jingxia Zhao, Jian Ni, Xiaoxv Dong
摘要
免疫疗法对肝细胞癌（HCC）的临床疗效受到肿瘤低免疫原性的限制。最近的研究表明，凋亡和光热治疗都可以有效地诱导肝癌细胞中的肿瘤免疫原性死亡（ICD）。 Polyphyllin II（PPII）是Paridis根瘤菌的主要活性成分，首次证明了肿瘤细胞中的凋亡，而IR780被808 nm激光激活，以将光能转化为热能，有效地消除了肿瘤细胞。但是，PPII和IR780都面临着诸如低溶解度和靶向较差的挑战，严重限制了它们的利用。为了解决这些问题，通过降水法将凋亡诱导剂PPII和光敏剂IR780共同加载在PLGA纳米颗粒中，并且在纳米颗粒的表面上修改了Aptamer AS1411，以构建靶向纳米颗粒（APT/PPII/IR780-NPS）。纳米颗粒具有pH/NIR双反应智能释放功能，该功能实现了靶向和受控药物在肿瘤部位的释放。此外，它可以迅速释放PPII以在激光照射下诱导细胞凋亡，并与基于IR780的光热疗法相结合，在体外和体内产生显着的协同抗肿瘤效应。该过程不仅促进了DC的成熟并激活效应T细胞，从而启动适应性免疫，而且还产生了持久和有效的免疫记忆。此外，APT/PPII/IR780-NP显着提高了抗PD-1功效。总而言之，基于APT/PPII/IR780-NP的化学治疗疗法可以显着增强肿瘤ICD，这为HCC免疫疗法提供了有希望的新策略。
Abstract
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.