A Multifunctional Nanocapsule Encapsulated with Artemisinin and Dual-Protease Activatable Probe for Imaging of Lysosomal Cancer Cell Death

【作者】 皇立卫； 罗荧萍； 田蒋为； 余伯阳；

【Author】 Liwei Huang;Yingping Luo;Jiangwei Tian;Bo-Yang Yu;State Key Laboratory of Natural Medicines, China Pharmaceutical University;Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Complex Prescription of TCM, China Pharmaceutical University;

【机构】 State Key Laboratory of Natural Medicines, China Pharmaceutical University； Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Complex Prescription of TCM, China Pharmaceutical University；

【摘要】 The nanomedicine has attracted considerable attentions due to its advantages of good biocompatibility,¹ enhanced therapeutic efficacy^2–4 and real-time evaluation of drug-induced cell death.^5,6 Here we utilize liposome functionalized with folate to encapsulate artemisinin and dual-protease activatable nanoprobe for manufacturing a multifunctional nanocapsule（MNC, Fig. 1）. The MNC can specifically recognize cancer cells and be selectively taken up by cancer cells via receptor-mediated endocytosis to enter lysosomes, in which artemisinin binds to lysosomal iron to produce reactive oxygen species（ROS）. The ROS specially damage the lysosomes and kill cancer cells in a lysosome-associated pathway. The dual-protease activatable probe can realize the detection of artemisinin into lysosome and monitoring of therapeutic response. Therefore, this work provides new insight into the lysosomal cancer cell death and design of multifunctional nanomedicine to promote the accuracy of cancer treatment.更多还原

【Abstract】 The nanomedicine has attracted considerable attentions due to its advantages of good biocompatibility,¹ enhanced therapeutic efficacy^2–4 and real-time evaluation of drug-induced cell death.^5,6 Here we utilize liposome functionalized with folate to encapsulate artemisinin and dual-protease activatable nanoprobe for manufacturing a multifunctional nanocapsule（MNC, Fig. 1）. The MNC can specifically recognize cancer cells and be selectively taken up by cancer cells via receptor-mediated endocytosis to enter lysosomes, in which artemisinin binds to lysosomal iron to produce reactive oxygen species（ROS）. The ROS specially damage the lysosomes and kill cancer cells in a lysosome-associated pathway. The dual-protease activatable probe can realize the detection of artemisinin into lysosome and monitoring of therapeutic response. Therefore, this work provides new insight into the lysosomal cancer cell death and design of multifunctional nanomedicine to promote the accuracy of cancer treatment.更多还原