Department of Dermatology, Xiangya Clinical Research Center for Cancer Immunotherapy, Hunan Key Laboratory of Skin Cancer and Psoriasis, Hunan Engineering Research Center of Skin Health and Disease, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
Department of Thoracic Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
J Mater Chem B. 2023 Sep 13;11(35):8492-8505. doi: 10.1039/d3tb00221g.
Tumor immunotherapy has been partly effective for specific cancers. However, problems such as low immune response, limited antitumor effectiveness, and high antibody costs still persist. Synergistic therapeutic approaches, such as immune checkpoint inhibition in conjunction with photothermal therapy and photoacoustic imaging, are expected to provide approaches for more precise and efficient immunotherapy of tumors. Furthermore, developing alternatives for antibodies, such as PD-L1 aptamers and nanocarriers, would reduce the cost of tumor immunotherapy. Herein, we develop a PD-L1-targeting nanotheranostic to block immune checkpoints for synergistic photothermal-immunotherapy against tumors, along with effective photoacoustic (PA) imaging. The nanotheranostic is synthesized by the modification of gold nanorods (GNRs) with the PD-L1 aptamer (APDL1), which can sensitively and specifically recognize PD-L1 on the tumor cell surface, and mediate nanoparticle accumulation and strong PA signals in tumors. The aptamer is released from GNR through a competition of glutathione (GSH) and is then functionalized as a PD-L1 blockade. In collaboration with the concurrent photothermal therapy, antitumor immunity is significantly augmented by enhancing the filtration of matured dendritic cells and suppressing regulatory T cells, followed by the activation of cytotoxic T cells and inhibition of T cell exhaustion. Such a nanotheranostic modality effectively suppresses tumor growth in mice, representing an appealing platform for both biological imaging and photoimmunotherapy of tumors.
肿瘤免疫疗法在某些特定癌症中已经取得了一定的疗效。然而，仍然存在一些问题，如免疫反应低、抗肿瘤效果有限以及抗体成本高。协同治疗方法，如免疫检查点抑制与光热疗法和光声成像相结合，有望为肿瘤的更精确和有效的免疫治疗提供方法。此外，开发抗体的替代品，如 PD-L1 适体和纳米载体，将降低肿瘤免疫治疗的成本。在此，我们开发了一种针对 PD-L1 的纳米治疗药物，用于阻断免疫检查点，以实现协同光热免疫治疗肿瘤，并具有有效的光声（PA）成像。该纳米治疗药物通过 PD-L1 适体（APDL1）修饰金纳米棒（GNR）合成，该适体能够敏感且特异性地识别肿瘤细胞表面的 PD-L1，并介导纳米颗粒在肿瘤中的积累和强烈的 PA 信号。通过谷胱甘肽（GSH）与金纳米棒的竞争，适体从金纳米棒上释放出来，然后被功能化为 PD-L1 阻断物。与同时进行的光热治疗协同作用，通过增强成熟树突状细胞的滤过作用和抑制调节性 T 细胞，随后激活细胞毒性 T 细胞并抑制 T 细胞耗竭，显著增强了抗肿瘤免疫。这种纳米治疗模式有效地抑制了小鼠肿瘤的生长，为肿瘤的生物成像和光免疫治疗提供了一种有吸引力的平台。
