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(SN₃₈-co-4-vinylpyridine) (termed AuNNP@PEG/PSN₃₈VP), showing intense PA signal in the NIR-II window. The effect of the rigidity of hydrophobic polymer PSN₃₈VP on the assembled structures and the formation mechanism of AuNNP@SN₃₈ 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/PSN₃₈VP. The hydrophilic AuNNP@PEG/PSN₃₈VP nanoparticles could penetrate deep into the tumor tissues and release the anticancer drug SN₃₈ 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.

中文翻译：

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第二近红外窗口光声成像引导的并行化学免疫治疗的生物反应性等离子组件。

我们开发了双重生物响应性纳米间隙金纳米颗粒囊泡，其中装有免疫抑制剂并携带抗癌聚合物前药，用于针对原发性和转移性肿瘤的协同同步化学免疫疗法，以及在第二个近红外（NIR）中通过光声（PA）成像引导货物释放-II）窗口。通过自组装接枝有聚乙二醇（PEG）和双重pH / GSH响应的聚产物聚（SN ₃₈ - co -4-乙烯基吡啶）（称为AuNNP @ PEG）的纳米金纳米颗粒（AuNNPs）自组装制备响应性囊泡/ PSN ₃₈ VP），在NIR-II窗口中显示出强烈的PA信号。疏水性聚合物PSN ₃₈的刚性影响通过计算仿真，阐明了AuNNP @ SN ₃₈ Ve组装结构的VP及其形成机理。免疫抑制剂BLZ-945封装在囊泡中，导致BLZ-945的pH响应释放，用于靶向免疫治疗，然后将囊泡解离为单个AuNNP @ PEG / PSN ₃₈ VP。亲水的AuNNP @ PEG / PSN ₃₈ VP纳米颗粒可以在还原环境下深入肿瘤组织并释放出抗癌药物SN ₃₈。在肿瘤深处的NIR-II窗口中获得了PA信号。装载BLZ-945的囊泡能够增强PA成像引导的同步化学免疫治疗功效，从而抑制原发性肿瘤和转移性肿瘤的生长。