Diao Shanchao, Zhang Zhifan, Zhao Sijun, Li Qiang, Zhang Xiaolong, Yang Xiangqi, Xu Zhiwei, Liu Mingming, Zhou Wen, Li Rutian, Xie Chen, Fan Quli
State Key Laboratory of Organic Electronics and Information Displays & Institute of Advanced Materials (IAM), Nanjing University of Posts & Telecommunications, 9 Wenyuan Road, Nanjing, 210023, China.
The Comprehensive Cancer Centre of Nanjing Drum Tower Hospital, the Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210008, China.
Adv Sci (Weinh). 2024 Dec;11(45):e2409833. doi: 10.1002/advs.202409833. Epub 2024 Oct 14.
Photodynamic immunotherapy which combines photodynamic therapy with immunotherapy has become an important and effective method for the treatment of cancer. However, most cancer photodynamic immunotherapeutic systems are not able to achieve precise release of immunomodulators, resulting in systemic side effects and poor patient outcomes. Herein, a dual-activatable nano-immunomodulator (DIR NP), which both its photodynamic effect and agonist release can be activated under specific stimuli, is reported for precision cancer photodynamic immunotherapy. The DIR NP is self-assembled from an R848-conjugated amphiphilic polymer (mPEG-TK-R848) and a hydrophobic oxidized bovine serum albumin (BSA-SOH)-conjugatable photosensitizer (DIR). DIR NPs may generate a small amount of O under 808 nm laser irradiation, leading to the cleavage of thioketal (TK) moiety and release of R848 and DIR. The released DIR may conjugate with tumor-overexpressed BSA-SOH, improving its photodynamic efficiency and NIR-II fluorescence signal. Such photodynamic efficiency improvement may further enhance the release of cargoes upon irradiation. The activated photodynamic effect induces immunogenic cell death (ICD) to release immune factors and R848 can enhance the maturation of dendritic cells for inhibiting the growth of both primary and distant tumors and eliminating lung metastasis. Therefore, this study provides a dual-activatable intelligent nano-immunomodulator for precise regulation of tumor photodynamic immunotherapy.
将光动力疗法与免疫疗法相结合的光动力免疫疗法已成为治疗癌症的一种重要且有效的方法。然而，大多数癌症光动力免疫治疗系统无法实现免疫调节剂的精确释放，导致全身副作用和患者预后不佳。在此，报道了一种双激活纳米免疫调节剂（DIR NP），其光动力效应和激动剂释放均可在特定刺激下被激活，用于精确的癌症光动力免疫治疗。DIR NP由R848共轭两亲聚合物（mPEG-TK-R848）和可与疏水性氧化牛血清白蛋白（BSA-SOH）共轭的光敏剂（DIR）自组装而成。在808 nm激光照射下，DIR NPs可能会产生少量的O，导致硫酮（TK）部分断裂并释放R848和DIR。释放的DIR可与肿瘤过表达的BSA-SOH共轭，提高其光动力效率和近红外二区荧光信号。这种光动力效率的提高可能会进一步增强照射后货物的释放。激活的光动力效应诱导免疫原性细胞死亡（ICD）以释放免疫因子，R848可增强树突状细胞的成熟，从而抑制原发性和远处肿瘤的生长并消除肺转移。因此，本研究提供了一种双激活智能纳米免疫调节剂，用于精确调控肿瘤光动力免疫治疗。
