用于肿瘤有效光声成像引导的光热免疫治疗的PD-L1靶向纳米治疗光声纳成像技术
A PD-L1 targeting nanotheranostic for effective photoacoustic imaging guided photothermal-immunotherapy of tumor.
发表日期:2023 Aug 18
作者:
Ruimin Chang, Tan Li, Yao Fu, Zeyu Chen, Yilang He, Xin Sun, Yiyi Deng, Yanqing Zhong, Zuozhong Xie, Yang Yang, Jing Liu, Xiang Chen, Hong Liu, Yuetao Zhao
来源:
Immunity & Ageing
摘要:
肿瘤免疫治疗对特定癌症部分有效。然而,低免疫反应、有限的抗肿瘤效果和高抗体成本等问题仍然存在。预计具有协同治疗效果的治疗方法,如联合免疫检查点抑制和光热治疗以及光声成像,将为肿瘤的精确和高效免疫治疗提供途径。此外,开发PD-L1适配体和纳米载体等抗体替代品将降低肿瘤免疫治疗的成本。本文中,我们开发了一种针对PD-L1的纳米治疗和诊断"治疗内诊疗",以阻止免疫检查点对肿瘤的协同光热免疫治疗,同时具备有效的光声成像功能。该纳米治疗和诊疗通过修饰金纳米棒(GNR)与PD-L1适配体(APDL1)相结合制备而成,该适配体可以灵敏且特异地识别肿瘤细胞表面的PD-L1,并在肿瘤中介导纳米颗粒的积累和强光声信号产生。通过谷胱甘肽(GSH)的竞争,适配体从GNR中被释放出来并作为PD-L1阻断剂进行功能化。与光热治疗同时进行,通过增强成熟树突状细胞的过滤和抑制调节性T细胞,显著增强了抗肿瘤免疫力,随之激活细胞毒性T细胞和抑制T细胞疲劳。这种纳米治疗和诊疗模式有效地抑制了小鼠肿瘤的生长,成为生物成像和肿瘤光免疫疗法吸引人的平台。
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.