New Strategies for Targeted Inducing and Real-Time Fluorescnece Imaging of Lysosomal Tumor Cell Death | Abstract
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Journal of Computational Methods in Molecular Design


New Strategies for Targeted Inducing and Real-Time Fluorescnece Imaging of Lysosomal Tumor Cell Death

Author(s): Jiangwei Tian

Despite rapid advances in diagnostic and therapeutic procedures, cancer remains one of the most deadly diseases in the world today. There is a strong need to identify new targets and develop novel approaches for the accurate cancer detection and targeted therapy. Lysosomes are critical organelles for cellular homeostasis and can be used as potential targets to kill tumor cells from inside. In the previous works, we have developed several photo-therapeutic methods 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. Here we reports a multifunctional nanoprobe to achieve targeted lysosomal tumor cell death without irradiation and real-time monitoring of drug-induced effect through encapsulating artemisinin and dual protease light-up nanoprobe in a transferrin-functionalized liposome. The nanoprobe can be specifically uptaken by tumor cells via transferrin receptor-mediated endocytosis to enter lysosomes, in which artemisinin reacts with affluent 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 nanoprobe for in vivo theranostics and may offer new opportunities for precise medicine.