Liu Qiang, Tian Jiangwei, Tian Ye, Sun Qinchao, Sun Dan, Wang Feifei, Xu Haijun, Ying Guoliang, Wang Jigang, Yetisen Ali K, Jiang Nan
Artemisinin Research Center and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
Department of Chemistry, Stanford University, Stanford, California 94305, United States.
ACS Nano. 2021 Jan 26;15(1):515-525. doi: 10.1021/acsnano.0c05317. Epub 2021 Jan 11.
Development of second near-infrared (NIR-II) nanoparticles (NPs) with high biocompatibility, low toxicity, and high singlet oxygen quantum yield (Φ) to prevent tumor recurrence is highly desirable in molecular imaging and photodynamic/immune combination therapy. Here, theranostic photosensitizer BODIPY (BDP)-I-N-anti-PD-L1 NPs were developed by encapsulating the photosensitizer BDP-I-N with amphipathic poly(styrene--chloromethylstyrene)--poly(ethylene glycol) nanocarriers through self-assembly functionalization with programmed cell death-ligand 1 (PD-L1) monoclonal antibody. These NPs exhibit highly intensive luminescence in the NIR-II window (1000-1700 nm) to real-time imaging of immune checkpoint PD-L1, high singlet oxygen quantum yield (Φ = 73%), and an eliminating effect of primary cancers. The NPs also allow for profiling PD-L1 expression as well as accumulating in MC38 tumor and enabling molecular imaging . Upon an 808 nm laser excitation, the targeted NPs produce an emission wavelength above 1200 nm to image a tumor to a normal tissue signal ratio (T/NT) at an approximate value of 14.1. Moreover, the MC38 tumors in mice are eliminated by combining photodynamic therapy and immunotherapy within 30 days, with no tumor recurrence within a period of 40 days. In addition, the tumors do not grow in the rechallenged mice within 7 days of inoculation. Such a strategy shows a durable immune memory effect against tumor rechallenging without toxic side effects to major organs.
开发具有高生物相容性、低毒性和高单线态氧量子产率（Φ）的第二代近红外（NIR-II）纳米颗粒（NPs）以预防肿瘤复发，在分子成像和光动力/免疫联合治疗中是非常可取的。在此，通过用程序性细胞死亡配体1（PD-L1）单克隆抗体进行自组装功能化，将光敏剂BDP-I-N封装在两亲性聚（苯乙烯-氯甲基苯乙烯）-聚（乙二醇）纳米载体中，制备了治疗诊断用光敏剂BODIPY（BDP）-I-N-抗PD-L1 NPs。这些纳米颗粒在NIR-II窗口（1000-1700nm）中表现出高强度发光，用于免疫检查点PD-L1的实时成像，具有高单线态氧量子产率（Φ = 73%），并对原发性癌症具有消除作用。这些纳米颗粒还能够分析PD-L1表达情况，并在MC38肿瘤中积累，实现分子成像。在808nm激光激发下，靶向纳米颗粒产生高于1200nm的发射波长，将肿瘤成像为正常组织信号比（T/NT），近似值为14.1。此外，通过在30天内联合光动力疗法和免疫疗法，可消除小鼠体内的MC38肿瘤，在40天内无肿瘤复发。此外，在再次接种的小鼠中，肿瘤在接种后7天内不会生长。这种策略显示出对肿瘤再次攻击具有持久的免疫记忆效应，且对主要器官无毒性副作用。
