Chen Qiaoqi, Yu Huilin, Li Lin, Zhang Hua, Tan Mixiao, Liu Weiwei, Zheng Min, Hu Yaqin, Cheng Long, Chen Yushi, Ran Haitao, Zeng Qiu, Guo Yuan
Department of Ultrasound, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China.
Chongqing Key Laboratory of Ultrasound Molecular Imaging and Therapy, Chongqing Medical University, Chongqing, 400010, China.
J Nanobiotechnology. 2025 Jun 21;23(1):459. doi: 10.1186/s12951-025-03536-2.
The stimulator of interferon genes (STING) pathway is a promising target in cancer immunotherapy. However, current nanomedicine strategies targeting the STING pathway often suffer from limited tumor specificity and insufficient immune activation. In this study, we developed a novel imaging-guided, self-amplifying photo-immunotherapeutic nanoparticle (SSCOL), comprising a liposome framework that encapsulates the phase-change material perfluoropentane (PFP), the photothermal agent superparamagnetic iron oxide (SPIO), and the STING agonist cGAMP. This nanoparticle exhibits excellent photoacoustic/ultrasound dual-modal imaging capability, enabling precise visualization of tumor tissue. CREKA enables specific binding to fibrin-fibronectin complexes in the tumor stroma, while NIR-induced photothermal effects of SPIO trigger coagulation, amplifying target formation and enhancing nanoparticle accumulation via a positive feedback mechanism. Under photothermal therapy, the phase transition of SSCOL enables the controlled and efficient release of the encapsulated cGAMP, which subsequently activates the STING pathway and triggers a pro-inflammatory cascade, enhances dendritic cell maturation and cytotoxic T lymphocyte activation, and elicits robust immune responses against both primary and metastatic tumors. Collectively, this multifunctional nanoparticle offers a promising strategy that integrates imaging, targeting, and photothermal-enhanced immune activation for STING-mediated cancer immunotherapy.
干扰素基因刺激物（STING）通路是癌症免疫治疗中一个很有前景的靶点。然而，目前靶向STING通路的纳米医学策略往往存在肿瘤特异性有限和免疫激活不足的问题。在本研究中，我们开发了一种新型的成像引导、自扩增光免疫治疗纳米颗粒（SSCOL），它由一个脂质体框架组成，该框架包裹了相变材料全氟戊烷（PFP）、光热剂超顺磁性氧化铁（SPIO）和STING激动剂cGAMP。这种纳米颗粒具有出色的光声/超声双模态成像能力，能够精确可视化肿瘤组织。CREKA能够特异性结合肿瘤基质中的纤维蛋白-纤连蛋白复合物，而SPIO的近红外诱导光热效应触发凝血，通过正反馈机制放大靶点形成并增强纳米颗粒的积累。在光热治疗下，SSCOL的相变能够实现对封装的cGAMP的可控和高效释放，随后激活STING通路并触发促炎级联反应，增强树突状细胞成熟和细胞毒性T淋巴细胞激活，并引发针对原发性和转移性肿瘤的强大免疫反应。总的来说，这种多功能纳米颗粒为STING介导的癌症免疫治疗提供了一种有前景的策略，该策略整合了成像、靶向和光热增强免疫激活。
