School of Engineering, China Pharmaceutical University, Nanjing, 211198, China.
School of Pharmaceutical Sciences, China Pharmaceutical University, Nanjing, 211198, China.
Biomater Sci. 2023 Mar 14;11(6):2167-2176. doi: 10.1039/d2bm01700h.
Frequency upconversion luminescence (FUCL) based on hot-band absorption has attracted considerable attention in bioimaging and phototherapy fields for deep-seated cancer treatment. Photoimmunotherapy, a promising therapeutic approach induced by photodynamic therapy (PDT), can selectively kill cancer cells, reverse the immunosuppressive system, boost host immune response, and elicit durable antitumor immunity. To date, few near-infrared organic photosensitizers for photodynamic immunotherapy have been reported based on hot-band absorption. Herein, we report an upconversion luminescent phthalocyanine photosensitizer PdPc(OBu) with anti-Stokes emission at 748 nm and highly efficient singlet oxygen generation with hot-band absorption at 808 nm. Taking advantage of nanoliposomes, FUCL phthalocyanine nano-photosensitizers (PdPc NPs) were obtained to reduce the aggregation-caused quenching and improve water solubility and biocompatibility. PdPc NPs could be effectively accumulated in tumor tissues through intravenous administration, causing FUCL-induced PDT under 808 nm irradiation. Considering its finite immune responses and tumor ablation after PDT, a combination of PdPc NP-based PDT with checkpoint inhibitors (anti-PD-L1) for near-infrared photoimmunotherapy has been used to potentiate the antitumor efficacy that could simultaneously ablate primary tumors and inhibit the progression of distant tumors. This study can promote the development of upconversion-based PDT combined with immunotherapy for tumor precision therapy.
基于热带吸收的上转换发光（FUCL）在生物成像和光疗领域中引起了相当大的关注，可用于深部癌症治疗。光免疫疗法是一种有前途的治疗方法，由光动力疗法（PDT）诱导，可选择性杀死癌细胞，逆转免疫抑制系统，增强宿主免疫反应，并引发持久的抗肿瘤免疫。迄今为止，基于热带吸收，很少有报道用于光动力免疫治疗的近红外有机光敏剂。在此，我们报告了一种上转换发光酞菁光敏剂 PdPc（OBu），它具有在 748nm 处的反斯托克斯发射和在 808nm 处高效的单重态氧产生的热带吸收。利用纳米脂质体，获得 FUCL 酞菁纳米光敏剂（PdPc NPs），以减少聚集引起的猝灭并提高水溶性和生物相容性。PdPc NPs 可以通过静脉注射有效积聚在肿瘤组织中，在 808nm 照射下引起 FUCL 诱导的 PDT。考虑到其有限的免疫反应和 PDT 后的肿瘤消融，PdPc NP 基 PDT 与检查点抑制剂（抗 PD-L1）联合用于近红外光免疫治疗已被用于增强抗肿瘤疗效，可同时消融原发性肿瘤并抑制远处肿瘤的进展。这项研究可以促进基于上转换的 PDT 与免疫疗法相结合用于肿瘤精准治疗的发展。
