Zhu Rong, Su Lichao, Dai Jiayong, Li Zhan-Wei, Bai Shumeng, Li Qingqing, Chen Xiaoyuan, Song Jibin, Yang Huanghao
MOE Key Laboratory for Analytical Science of Food Safety and Biology, College of Chemistry, Fuzhou University, Fuzhou 350116, China.
State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China.
ACS Nano. 2020 Apr 28;14(4):3991-4006. doi: 10.1021/acsnano.9b07984. Epub 2020 Mar 30.
We developed dual biologically responsive nanogapped gold nanoparticle vesicles loaded with immune inhibitor and carrying an anticancer polymeric prodrug for synergistic concurrent chemo-immunotherapy against primary and metastatic tumors, along with guided cargo release by photoacoustic (PA) imaging in the second near-infrared (NIR-II) window. The responsive vesicle was prepared by self-assembly of nanogapped gold nanoparticles (AuNNPs) grafted with poly(ethylene glycol) (PEG) and dual pH/GSH-responsive polyprodug poly(SN--4-vinylpyridine) (termed AuNNP@PEG/PSNVP), showing intense PA signal in the NIR-II window. The effect of the rigidity of hydrophobic polymer PSNVP on the assembled structures and the formation mechanism of AuNNP@SN Ve were elucidated by computational simulations. The immune inhibitor BLZ-945 was encapsulated into the vesicles, resulting in pH-responsive release of BLZ-945 for targeted immunotherapy, followed by the dissociation of the vesicles into single AuNNP@PEG/PSNVP. The hydrophilic AuNNP@PEG/PSNVP nanoparticles could penetrate deep into the tumor tissues and release the anticancer drug SN under the reductive environment. A PA signal in the NIR-II window in the deep tumor region was obtained. The BLZ-945-loaded vesicle enabled enhanced PA imaging-guided concurrent chemo-immunotherapy efficacy, inhibiting the growth of both primary tumors and metastatic tumors.
我们开发了一种双生物响应性纳米间隙金纳米颗粒囊泡，其负载免疫抑制剂并携带抗癌聚合物前药，用于对原发性和转移性肿瘤进行协同同步化学免疫治疗，同时通过近红外二区（NIR-II）窗口的光声（PA）成像实现靶向药物释放。这种响应性囊泡是由接枝聚乙二醇（PEG）的纳米间隙金纳米颗粒（AuNNPs）和双pH/谷胱甘肽（GSH）响应性聚前药聚（S-4-乙烯基吡啶）（称为AuNNP@PEG/PSNVP）自组装而成，在NIR-II窗口显示出强烈的PA信号。通过计算模拟阐明了疏水性聚合物PSNVP的刚性对组装结构的影响以及AuNNP@SN Ve的形成机制。将免疫抑制剂BLZ-945封装到囊泡中，实现了BLZ-945的pH响应性释放以进行靶向免疫治疗，随后囊泡解离为单个AuNNP@PEG/PSNVP。亲水性AuNNP@PEG/PSNVP纳米颗粒可深入肿瘤组织，并在还原环境下释放抗癌药物SN。在深部肿瘤区域获得了NIR-II窗口的PA信号。负载BLZ-945的囊泡实现了增强的PA成像引导同步化学免疫治疗效果，抑制了原发性肿瘤和转移性肿瘤的生长。
