光热疗法(PTT),它利用光热剂的高热转化能力在高温下消融肿瘤细胞,由于其具有高选择性和特异性等优点,精确靶向肿瘤部位,低侵袭性和创伤。然而,由NIR-I引导的PTT在组织穿透深度方面具有局限性,导致对深部肿瘤组织的影像学监测和治疗效果有限。此外,在治疗过程中,纳米粒子容易被免疫系统清除,难以被动靶向肿瘤部位。为了解决这些问题,我们使用NIR-II染料IR1048和DSPE-PEG-OH制备了纳米颗粒,并将它们进一步包裹在小鼠的红细胞膜中。这些仿生纳米粒子,称为RDIR1048,显示免疫系统的清除率降低,并具有长循环特征。它们有效地积累在肿瘤部位,给药后96小时,在肿瘤部位仍可观察到强烈的荧光。此外,通过小鼠热成像实验,我们发现RDIR1048表现出良好的PTT能力。当与免疫检查点抑制剂联合使用时,抗PD-L1抗体,它增强了由PTT引起的肿瘤细胞的免疫原性细胞死亡,提高了免疫治疗的治疗效果,在荷瘤小鼠的治疗中表现出良好的治疗效果。本研究为今后开发具有长环流性质的NIR-Ⅱ纳米粒子提供了可行的依据。
Photothermal therapy (PTT), which uses the high thermal conversion ability of photothermal agents to ablate tumor cells at high temperatures, has gained significant attention because it has the advantages of high selectivity and specificity, precise targeting of tumor sites, and low invasiveness and trauma. However, PTT guided by the NIR-I has limitations in tissue penetration depth, resulting in limited imaging monitoring and therapeutic effects on deep-seated tumor tissues. Moreover, nanoparticles are easily cleared by the immune system and difficult to passively target tumor sites during the process of treatment. To address these issues, we prepared nanoparticles using NIR-II dyes IR1048 and DSPE-PEG-OH and further encapsulated them in red blood cell membranes derived from mice. These biomimetic nanoparticles, called RDIR1048, showed reduced clearance by the immune system and had long circulation characteristics. They effectively accumulated at tumor sites, and strong fluorescence could still be observed at the tumor site 96 h after administration. Furthermore, through mouse thermal imaging experiments, we found that RDIR1048 exhibited good PTT ability. When used in combination with an immune checkpoint inhibitor, anti-PD-L1 antibodies, it enhanced the immunogenic cell death of tumor cells caused by PTT and improved the therapeutic effect of immunotherapy, which demonstrated good therapeutic efficacy in the treatment of tumor-bearing mice. This study provides a feasible basis for the future development of NIR-II nanoparticles with long circulation properties.