School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu 210009, China.
School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.
J Control Release. 2024 Apr;368:780-796. doi: 10.1016/j.jconrel.2024.03.026. Epub 2024 Mar 20.
Designing effective nanomedicines to induce durable anti-tumor immunity represents a promising strategy for improving moderate immune stimulation. In this study, we engineered a multifunctional nanoreactor (named SCGFP NPs) for remodeling the tumor microenvironment (TME) to improve the therapeutic efficacy of immunotherapy. The core of SCGFP NPs consists of CaCO loaded with SN38, prepared by the gas diffusion method, and coated with a significant amount of gallic acid-Fe-PEG coordination polymer on the surface. In the acidic TME, SCGFP NPs explosively release exogenous Ca and SN38. The SN38-induced intracellular Ca accumulation and exogenous Ca synergistically trigger immunogenic cell death (ICD) through sustained Ca overload. The ablation of tumors with high-intensity photothermal therapy (PTT) by near-infrared (NIR) irradiation of GA-Fe induces tumor cell necrosis, further enhancing ICD activation. Additionally, SN38 upregulates PD-L1, amplifying tumor responsiveness to immune checkpoint inhibitors (ICIs). This study indicates that SCGFP NPs, through the integration of a trimodal therapeutic strategy, hold enormous potential for various types of tumor immunotherapy through distinct mechanisms or synergistic effects.
设计有效的纳米药物以诱导持久的抗肿瘤免疫反应代表了一种改善适度免疫刺激的有前途的策略。在这项研究中，我们设计了一种多功能纳米反应器（命名为 SCGFP NPs），用于重塑肿瘤微环境（TME），以提高免疫疗法的治疗效果。SCGFP NPs 的核心由通过气体扩散法制备的负载 SN38 的 CaCO3 组成，并在表面涂覆大量没食子酸-Fe-PEG 配位聚合物。在酸性 TME 中，SCGFP NPs 会爆炸性地释放外源性 Ca 和 SN38。SN38 诱导的细胞内 Ca 积累和外源性 Ca 协同通过持续的 Ca 过载触发免疫原性细胞死亡（ICD）。通过近红外（NIR）辐照 GA-Fe 进行高强度光热治疗（PTT）消融肿瘤，进一步增强 ICD 激活。此外，SN38 上调 PD-L1，增强肿瘤对免疫检查点抑制剂（ICIs）的反应性。这项研究表明，SCGFP NPs 通过整合三模态治疗策略，通过不同的机制或协同作用，为各种类型的肿瘤免疫治疗提供了巨大的潜力。
