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Tumor microenvironment-responsive size-changeable and biodegradable HA-CuS/MnO2 nanosheets for MR imaging and synergistic chemodynamic therapy/phototherapy

Zhen Jin,Yunkai Wang,Miaomiao Han,Li Wang,Fei Lin,Qianfang Jia,Wu Ren,Jiawei Xu,Wenhao Yang,Guo-an Zhao,Xuming Sun,Changqin Jing

Tumor microenvironment (TME)-responsive size-changeable and biodegradable nanoplatforms for multimodal therapy possess huge advantages in anti-tumor therapy. Hence, we developed a hyaluronic acid (HA) modified CuS/MnO 2 nanosheets (HCMNs) as a multifunctional nanoplatform for synergistic chemodynamic therapy (CDT)/photothermal therapy (PTT)/photodynamic therapy (PDT). The prepared HCMNs exhibited significant NIR light absorption and photothermal conversion efficiency because of the densely deposited ultra-small sized CuS nanoparticles on the surface of MnO 2 nanosheet. They could precisely target the tumor cells and rapidly decomposed into small sized nanostructures in the TME, and then efficiently promote intracellular ROS generation through a series of cascade reactions. Moreover, the local temperature elevation induced by photothermal effect also promote the PDT based on CuS nanoparticles and the Fenton-like reaction of Mn 2+ , thereby enhancing the therapeutic efficiency. Furthermore, the T 1 -weighted magnetic resonance (MR) imaging was significantly enhanced by the abundant Mn 2+ ions from the decomposition process of HCMNs. In addition, the CDT/PTT/PDT synergistic therapy using a single NIR light source exhibited considerable anti-tumor effect via in vitro cell test. Therefore, the developed HCMNs will provide great potential for MR imaging and multimodal synergistic cancer therapy.