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Light‐Induced ROS Generation and 2‐DG‐Activated Endoplasmic Reticulum Stress by Antitumor Nanosystems: An Effective Combination Therapy by Regulating the Tumor Microenvironment
Authors:Mei Dong  Xuan‐Zhong Xiao  Zhi‐Gui Su  Zheng‐Hang Yu  Cheng‐Gen Qian  Jia‐Hao Liu  Jia‐Cheng Zhao  Qun‐Dong Shen
Abstract:A multimodal cancer therapeutic nanoplatform is reported. It demonstrates a promising approach to synergistically regulating the tumor microenvironment. The combination of intracellular reactive oxygen species (ROS) generated by irradiation of photosensitizer and endoplasmic reticulum (ER) stress induced by 2‐deoxy‐glucose (2‐DG) has a profound effect on necrotic or apoptotic cell death. Especially, targeting metabolic pathway by 2‐DG is a promising strategy to promote the effect of photodynamic therapy and chemotherapy. The nanoplatform can readily release its cargoes inside cancer cells and combines the advantages of ROS‐sensitive releasing chemotherapeutic drugs, upregulating apoptosis pathways under ER stress, light‐induced generation of cytotoxic ROS, achieving tumor accumulation, and in vivo fluorescence imaging capability. This work highlights the importance of considering multiple intracellular stresses as design parameters for nanoscale functional materials in cell biology, immune response, as well as medical treatments of cancer, Alzheimer's disease, etc.
Keywords:combination cancer therapy  endoplasmic reticulum stress  photodynamic therapy  ROS‐triggered nanoplatforms  tumor microenvironment synergistical regulation
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