PDF(Pubmed)
Abstract：
The hypoxic tumor microenvironment (TME) of osteosarcoma (OS) is the Achilles\' heel of oxygen-dependent photodynamic therapy (PDT), and tremendous challenges are confronted to reverse the hypoxia. Herein, we proposed a \"reducing expenditure of O2 and broadening sources\" dual-strategy and constructed ultrasmall IrO2@BSA-ATO nanogenerators (NGs) for decreasing the O2-consumption and elevating the O2-supply simultaneously. As O2 NGs, the intrinsic catalase (CAT) activity could precisely decompose the overexpressed H2O2 to produce O2 in situ, enabling exogenous O2 infusion. Moreover, the cell respiration inhibitor atovaquone (ATO) would be at the tumor sites, effectively inhibiting cell respiration and elevating oxygen content for endogenous O2 conservation. As a result, IrO2@BSA-ATO NGs systematically increase tumor oxygenation in dual ways and significantly enhance the antitumor efficacy of PDT. Moreover, the extraordinary photothermal conversion efficiency allows the implementation of precise photothermal therapy (PTT) under photoacoustic guidance. Upon a single laser irradiation, this synergistic PDT, PTT, and the following immunosuppression regulation performance of IrO2@BSA-ATO NGs achieved a superior tumor cooperative eradicating capability both in vitro and in vivo. Taken together, this study proposes an innovative dual-strategy to address the serious hypoxia problem, and this microenvironment-regulable IrO2@BSA-ATO NGs as a multifunctional theranostics platform shows great potential for OS therapy.
摘要：
骨肉瘤(OS)的缺氧肿瘤微环境(TME)是氧依赖性光动力疗法(PDT)的致命弱点,扭转缺氧面临巨大挑战。在这里，我们提出了“减少O2消耗并扩大来源”的双重策略，并构造了超小型IrO2@BSA-ATO纳米发电机（NG），以减少O2消耗并同时提高O2供应。作为O2NGs，内源性过氧化氢酶（CAT）活性可以精确分解过表达的H2O2，原位产生O2，使外源性O2输注。此外，细胞呼吸抑制剂atovaquone（ATO）将在肿瘤部位，有效抑制细胞呼吸，提高氧含量，以保持内源性O2。因此,IrO2@BSA-ATONG以双重方式系统地增加肿瘤氧合，并显着增强PDT的抗肿瘤功效。此外，非凡的光热转换效率允许在光声引导下实施精确的光热治疗(PTT)。在单次激光照射下，这种协同的PDT，PTT,IrO2@BSA-ATONG的以下免疫抑制调节性能在体外和体内均实现了优异的肿瘤协同根除能力。一起来看,这项研究提出了一种创新的双重策略来解决严重的缺氧问题，这种微环境可调节的IrO2@BSA-ATONG作为多功能治疗平台显示出OS治疗的巨大潜力。
