Department of Nuclear Medicine, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing University, Jiangsu 210008, PR China; Department of Radiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing University, Jiangsu 210008, PR China; Department of Hematology, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Jiangsu 225001, PR China.
Department of Endocrinology, Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Jiangsu 225001, PR China.
Acta Biomater. 2018 Oct 15;80:296-307. doi: 10.1016/j.actbio.2018.09.017. Epub 2018 Sep 15.
WO-mediated photodynamic therapy (PDT) and photothermal therapy (PTT) are limited by the easily oxidized property and tumor hypoxia. Here, we report the development of platelet membranes as nanocarriers to co-load WO nanoparticles (NPs) and metformin (PM-WO-Met NPs). Platelet membranes can protect WO from oxidation and immune evasion, and increase the accumulation of WO in tumor sites via the passive EPR effect and active adhesion between platelets and cancer cells. The introduction of metformin (Met), a typical anti-diabetic drug, can alleviate the tumor hypoxia through reducing oxygen consumption. As a result, ROS and heat generation are both greatly increased, as revealed by ROS/hypoxia imaging in vitro, IR thermal imaging in vivo and PET imaging in vivo. PM-WO-Met NPs show the improved therapeutic effects with greatly inhibited tumor growth and induced tumor cell apoptosis. Therefore, our work provides a novel strategy for simultaneous enhanced PDT and PTT, which is promising in bioapplication. STATEMENTE OF SIGNIFICANCE: WO-mediated photodynamic therapy and photothermal therapy are limited by the poor delivery of nanoparticles to tumors, the easily oxidized property, and tumor hypoxia environment, which will induce tumor treatment failure. Herein, we report the development of platelet membranes as nanocarriers to co-load WO nanoparticles and metformin (PM-WO-Met NPs). Platelet membranes can protect WO from oxidation and immune evasion, and increase the accumulation of WO in tumor sites via the passive EPR effect and active adhesion. Metformin can alleviate the tumor hypoxia through reducing oxygen consumption. Hence, ROS and heat generation are both greatly increased. PM-WO-Met NPs show the improved therapeutic effects with greatly inhibited tumor growth and induced apoptosis. Therefore, our work provides a novel strategy in bioapplication.
WO 介导的光动力疗法（PDT）和光热疗法（PTT）受到纳米颗粒易氧化和肿瘤乏氧的限制。在此，我们报告了血小板膜作为纳米载体来共载 WO 纳米颗粒（NPs）和二甲双胍（PM-WO-Met NPs）的发展。血小板膜可以保护 WO 免受氧化和免疫逃避，并通过被动 EPR 效应和血小板与癌细胞之间的主动黏附增加 WO 在肿瘤部位的积累。二甲双胍（Met）的引入，一种典型的抗糖尿病药物，可以通过减少耗氧量来缓解肿瘤缺氧。结果，ROS 和产热都大大增加，体外 ROS/缺氧成像、体内 IR 热成像和体内 PET 成像都揭示了这一点。PM-WO-Met NPs 表现出改善的治疗效果，大大抑制了肿瘤生长并诱导肿瘤细胞凋亡。因此，我们的工作为同时增强 PDT 和 PTT 提供了一种新的策略，在生物应用中具有广阔的前景。
