Institute of Nano Biomedicine and Engineering, Shanghai Engineering Research Center for Intelligent Diagnosis and Treatment Instrument, Department of Instrument Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, 800 Dongchuan RD, Shanghai, 200240, P. R. China.
National Center for Translational Medicine, Collaborative Innovational Center for System Biology, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai, 200240, P. R. China.
Adv Mater. 2023 Nov;35(45):e2303722. doi: 10.1002/adma.202303722. Epub 2023 Oct 10.
Nanozymes with inherent enzyme-mimicking catalytic properties combat malignant tumor progression via catalytic therapy, while the therapeutic efficacy still needs to be improved. In this work, ultrasmall platinum nanozymes (nPt) in a confined domain of a wormlike pore channel in gold nanobipyramidal-mesoporous silica dioxide nanocomposites, producing nanozyme carriers AP-mSi with photoenhanced peroxidase ability, are innovatively synthesized. Afterward, based on the prepared AP-mSi, a lung-cancer nanozymes probe (AP-HAI) is ingeniously produced by removing the SiO template, modifying human serum albumin, and loading atovaquone molecules (ATO) as well as IR780. Under NIR light irradiation, inner AuP and IR780 collaborate for photothermal process, thus facilitating the peroxidase-like catalytic process of H O . Additionally, loaded ATO, a cell respiration inhibitor, can impair tumor respiration metabolism and cause oxygen retention, hence enhancing IR780's photodynamic therapy (PDT) effectiveness. As a result, IR780's PDT and nPt nanozymes' photoenhanced peroxidase-like ability endow probes a high ROS productivity, eliciting antitumor immune responses to destroy tumor tissue. Systematic studies reveal that the obvious reactive oxygen species (ROS) generation is obtained by the strategy of using nPt nanozymes and reducing oxygen consumption by ATO, which in turn enables lung-cancer synergetic catalytic therapy/immunogenic-cell-death-based immunotherapy. The results of this work would provide theoretical justification for the practical use of photoenhanced nanozyme probes.
具有固有酶模拟催化特性的纳米酶通过催化治疗来对抗恶性肿瘤的进展,但其治疗效果仍有待提高。在这项工作中,创新性地合成了在金纳米双锥-介孔二氧化硅纳米复合材料的蠕虫状孔道受限域内具有类过氧化物酶能力的超小铂纳米酶(nPt),作为纳米酶载体 AP-mSi。随后,基于制备的 AP-mSi,通过去除 SiO 模板、修饰人血清白蛋白并装载阿托伐醌(ATO)和 IR780,巧妙地制备了肺癌纳米酶探针(AP-HAI)。在近红外光照射下,内 AuP 和 IR780 协同进行光热过程,从而促进 H2O2 的过氧化物酶样催化过程。此外,负载的细胞呼吸抑制剂 ATO 可损害肿瘤呼吸代谢并导致氧气滞留,从而增强 IR780 的光动力治疗(PDT)效果。因此,IR780 的 PDT 和 nPt 纳米酶的光增强过氧化物酶样能力赋予探针高 ROS 产生能力,引发抗肿瘤免疫反应来破坏肿瘤组织。系统研究表明,通过使用 nPt 纳米酶和减少 ATO 消耗来产生明显的活性氧(ROS),从而实现肺癌协同催化治疗/基于免疫细胞死亡的免疫治疗。这项工作的结果将为光增强纳米酶探针的实际应用提供理论依据。