An artemisinin-mediated ROS evolving and dual protease light-up nanocapsule for real-time imaging of lysosomal tumor cell death.
Lysosomes are critical organelles for cellular homeostasis and can be used as potential targets to kill tumor cells from inside. Many photo-therapeutic methods have been developed to overproduce reactive oxygen species (ROS) to trigger lysosomal membrane permeabilization (LMP)-associated cell death pathway. However, these technologies rely on extra irradiation to activate the photosensitizers, which limits the applications in treating deep seated tumors and widespread metastatic lesions. This work reports a multifunctional nanocapsule to achieve targeted lysosomal tumor cell death without irradiation and real-time monitoring of drug effect through encapsulating artemisinin and dual protease light-up nanoprobe in a folate-functionalized liposome. The nanocapsule can be specifically uptaken by tumor cells via folate receptor-mediated endocytosis to enter lysosomes, in which artemisinin reacts with ferrous to generate ROS for LMP-associated cell death. By virtue of confocal fluorescence imaging, the artemisinin location in lysosome, ROS-triggered LMP and ultimate cell apoptosis can be visualized with the cathepsin B and caspase-3 activatable nanoprobe. Notably, the artemisinin-mediated ROS evolving for tumor therapy and real-time therapeutic monitoring were successfully implemented by living imaging in tumor-bearing mice, which broaden the nanocapsule for in vivo theranostics and may offer new opportunities for precise medicine.
Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Complex Prescription of TCM, China Pharmaceutical University, Nanjing 211198, PR China.
Liwei
L
Huang
Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Complex Prescription of TCM, China Pharmaceutical University, Nanjing 211198, PR China.
Yingping
Y
Luo
Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Complex Prescription of TCM, China Pharmaceutical University, Nanjing 211198, PR China.
Xian
X
Sun
State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, PR China.
Huangxian
H
Ju
State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, PR China; Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Complex Prescription of TCM, China Pharmaceutical University, Nanjing 211198, PR China; College of Chemistry, Chemical Engineering and Materials Science, Shandong Provincial Key Laboratory of Clean Production of Fine Chemicals, Shandong Normal University, 250014, PR China. Electronic address: jwtian@cpu.edu.cn.
Jiangwei
J
Tian
State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, PR China; Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Complex Prescription of TCM, China Pharmaceutical University, Nanjing 211198, PR China. Electronic address: boyangyu59@163.com.
Bo-Yang
BY
Yu
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D037621:Artemisinins / Q000008:administration & dosage / Q000378:metabolism*; D015374:Biosensing Techniques; D053148:Caspase 3 / Q000378:metabolism; D002401:Cathepsin B / Q000378:metabolism; D045744:Cell Line, Tumor; D006367:HeLa Cells; D006801:Humans; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018613:Microscopy, Confocal / Q000379:methods*; D053769:Nanocapsules / Q000737:chemistry; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology*; D061848:Optical Imaging / Q000379:methods*; D010539:Permeability / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism*
D037621:Artemisinins; D053769:Nanocapsules; D017382:Reactive Oxygen Species; C031327:artemisinin; D053148:Caspase 3; D002401:Cathepsin B
Artemisinin; Fluorescence imaging; Lysosome; Nanomedicine; Reactive oxygen species; Tumor