基于纳米酶的化学动力学疗法(CDT)在治疗细菌感染方面显示出巨大的潜力。然而,CDT抗菌功效受到纳米酶的催化活性或感染微环境如过氧化氢(H2O2)不足和过表达的谷胱甘肽(GSH)的严重限制。在这里,通过简单地通过共价Cu-S键将超小的CuO2纳米点装饰在绣球花状MoS2纳米载体的层状MoS2血小板上,可以合理地构建通用的杂合纳米酶(MoS2/CuO2)。MoS2/CuO2纳米酶表现出过氧化物酶模拟活性,可将修饰的CuO2的酸触发分解产生的H2O2催化转化为羟基自由基(•OH)。同时,MoS2/CuO2可以通过多价过渡金属离子(Cu2和Mo6)介导的氧化还原反应消耗在感染部位过表达的GSH,以增强CDT。更重要的是,MoS2载体可以通过基于Mo4/Mo6氧化还原对的共催化反应促进Cu2转化为Cu,并提供光子热疗(PTT)以增强过氧化物酶模拟活性。开发的MoS2/CuO2纳米酶具有理想的催化性能,以及在体外和体内显著提高的抗菌效率。一起来看,这项研究提出了一种协同的多重增强策略,以成功构建用于强化体内PTT/CDT双模式抗感染治疗的多功能杂合纳米酶。重要性声明:化学动力学疗法(CDT)在治疗细菌感染方面显示出巨大的潜力,而其治疗效率受到感染微环境的严重限制,例如过氧化氢(H2O2)不足和谷胱甘肽(GSH)过表达。这里,我们合理地构建了一种具有过氧化物酶样活性的杂合纳米酶(MoS2/CuO2),可以通过调节局部微环境来增强CDT,也就是说,同时自我供应H2O2和消耗GSH。重要的是,MoS2载体可以通过Mo4/Mo6氧化还原对促进Cu2转化为Cu,并提供光子热疗(PTT)以增强过氧化物酶模拟活性。开发的MoS2/CuO2在体外和体内均显示出期望的PTT/CDT双模式抗菌功效。本研究提出了一种具有多种增强作用的多功能杂合纳米酶,用于体内强化抗感染治疗。
Nanozyme-based chemodynamic therapy (
CDT) has shown tremendous potential in the treatment of bacterial infections. However, the
CDT antibacterial efficacy is severely limited by the catalytic activity of nanozymes or the infection microenvironments such as insufficient hydrogen peroxide (H2O2) and overexpressed glutathione (GSH). Herein, a versatile hybrid nanozyme (MoS2/CuO2) is rationally constructed by simply decorating ultrasmall CuO2 nanodots onto lamellar MoS2 platelets of hydrangea-like MoS2 nanocarrier via a covalent Cu-S bond. The MoS2/CuO2 nanozyme exhibits the peroxidase-mimic activity for catalytically converting H2O2 produced by acid-triggered decomposition of the decorated CuO2 into hydroxyl radical (•OH). Meanwhile, the MoS2/CuO2 can consume GSH overexpressed in the infection sites via redox reaction mediated by polyvalent transition metal ions (Cu2+ and Mo6+) for enhanced
CDT. More importantly, MoS2 support can promote the conversion of Cu2+ to Cu+ by a co-catalytic reaction based on the Mo4+/Mo6+ redox couples, and provide photonic hyperthermia (PTT) to augment the peroxidase-mimic activity. The developed MoS2/CuO2 nanozymes possesses a desirable catalytic property, as well as a remarkably improved antibacterial efficiency both in vitro and in vivo. Taken together, this study proposes a synergetic multiple enhancement strategy to successfully construct the versatile hybrid nanozymes for intensive in vivo PTT/CDT dual-mode anti-infective therapy. STATEMENT OF SIGNIFICANCE: Chemodynamic therapy (
CDT) has shown great potentialities in the treatment of bacterial infections, while its therapeutic efficiency is severely limited by the infection microenvironments such as insufficient hydrogen peroxide (H2O2) and overexpressed glutathione (GSH). Here, we rationally construct a hybrid nanozyme (MoS2/CuO2) with peroxidase-like activity that can enhance CDT by regulating local microenvironments, that is, simultaneously self-supplying H2O2 and consuming GSH. Importantly, MoS2 support can promote the conversion of Cu2+ to Cu+ by the Mo4+/Mo6+ redox couples, and provide photonic hyperthermia (PTT) to augment the peroxidase-mimic activity. The developed MoS2/CuO2 shows desirable PTT/
CDT dual-mode antibacterial efficacy both in vitro and in vivo. This study proposes a versatile hybrid nanozyme with multiple enhancement effects for intensive in vivo anti-infective therapy.