Faculty of Materials Science and Chemistry, China University of Geosciences, Wuhan, 430074, P. R. China.
Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430034, P. R. China.
Adv Healthc Mater. 2024 Feb;13(4):e2302156. doi: 10.1002/adhm.202302156. Epub 2023 Nov 2.
Surgery is a traditional tumor treatment, and immunotherapy can reduce the postoperative recurrence of tumors. However, the intrinsic limits of low responsive rate and non-tumor specificity of immunotherapy agents are still insufficient to address therapeutic demands. Herein, the macrophages membrane camouflaged nanoparticles (NPs), named M@PFC, consisting of the aggregation-induced emission photosensitizer (PF3-PPh ) and immune adjuvant (CpG), are reported. As the protein on the membrane interacts with the vascular cell adhesion molecule 1 (VCAM-1) of cancer cells, M@PFC efficiently transports CpG to the tumor. Meanwhile, M@PFC can evade clearance by the immune system and prolong the circulation time in vivo; thus, enhancing their accumulation in tumors. PF3-PPh promotes high production of reactive oxygen species (ROS) and triggers immune cell death (ICD) in tumor cells under light exposure. Importantly, CpG enrichment in tumors can stimulate tumor cells to produce immune factors to assist in enhancing ICD effects. The synergistic effect combining the PDT properties of the aggregation-induced emission (AIE)-active photosensitizer and immunotherapy properties of CpG significantly delays tumor recurrence after surgery. In conclusion, this strategy achieves the synergistic activation of the immune system for anti-tumor activity, providing a novel paradigm for the development of therapeutic nanodrugs to delay postoperative tumor recurrence.
手术是一种传统的肿瘤治疗方法,免疫疗法可以降低肿瘤的术后复发率。然而,免疫疗法药物固有反应率低和非肿瘤特异性的内在限制仍然不足以满足治疗需求。在此,报道了一种由聚集诱导发射光敏剂(PF3-PPh)和免疫佐剂(CpG)组成的巨噬细胞膜伪装纳米颗粒(M@PFC)。由于膜上的蛋白质与癌细胞的血管细胞黏附分子 1(VCAM-1)相互作用,M@PFC 可以有效地将 CpG 递送到肿瘤部位。同时,M@PFC 可以逃避免疫系统的清除,并延长体内的循环时间;从而增强其在肿瘤中的积累。在光照下,PF3-PPh 促进大量活性氧(ROS)的产生,并引发肿瘤细胞中的免疫细胞死亡(ICD)。重要的是,肿瘤中 CpG 的富集可以刺激肿瘤细胞产生免疫因子,以协助增强 ICD 效应。聚集诱导发射(AIE)活性光敏剂的 PDT 特性和 CpG 的免疫治疗特性的协同作用显著延缓了手术后肿瘤的复发。总之,该策略实现了免疫系统对抗肿瘤活性的协同激活,为开发用于延迟术后肿瘤复发的治疗性纳米药物提供了新的范例。