Multimodal lung cancer theranostics via manganese phosphate/quercetin particle
Chong Qiu, Fei Xia, Qingchao Tu, Huan Tang, Yinan Liu, Hongda Liu, Chen Wang, HaiLu Yao, Lin Zhong, Yuanfeng Fu, Pengbo Guo, Weiqi Chen, Xinyu Zhou, Lili Zou, Licheng Gan, Jiawei Yan, Yichong Hou, Junzhe Zhang, Huanhuan Pang, Yuqing Meng, Qiaoli Shi, Guang Han, Xijun Wang, Jigang Wang
Abstract
The diagnosis and treatment of non-small cell lung cancer in clinical settings face serious challenges, particularly due to the lack of integration between the two processes, which limit real-time adjustments in treatment plans based on the patient’s condition and drive-up treatment costs. Here, we present a multifunctional pH-sensitive core-shell nanoparticle containing quercetin (QCT), termed AHA@MnP/QCT NPs, designed for the simultaneous diagnosis and treatment of non-small cell lung cancer. Mechanistic studies indicated that QCT and Mn2+ exhibited excellent peroxidase-like (POD-like) activity, catalysing the conversion of endogenous hydrogen peroxide into highly toxic hydroxyl radicals through a Fenton-like reaction, depleting glutathione (GSH), promoting reactive oxygen species (ROS) generation in mitochondria and endoplasmic reticulum, and inducing ferroptosis. Additionally, Mn2+ could activate the cGAS-STING signalling pathway and promote the maturation of dendritic cells and infiltration of activated T cells, thus inducing tumor immunogenic cell death (ICD). Furthermore, it exhibited effective T2-weighted MRI enhancement for tumor imaging, making them valuable for clinical diagnosis. In vitro and in vivo experiments demonstrated that AHA@MnP/QCT NPs enabled non-invasive imaging and tumor treatment, which presented a one-stone-for-two-birds strategy for combining tumor diagnosis and treatment, with broad potential for clinical application in non-small cell lung cancer therapy.