Nanoparticles (NPs)-mediated targeted regulation of redox homeostasis for effective cancer therapy
Zixuan Zhao, Yuan Cao, Rui Xu, Junyue Fang, Yuxuan Zhang, Xiaoding Xu, Linzhuo Huang, Rong Li
Abstract
Although characterized by high reactive oxygen species (ROS) generation, cancer cells maintain redox homeostasis to avoid severe damage ( e.g. , DNA, protein, and plasma membrane dysfunction) and facilitate cancer progression. Emerging evidence has indicated that targeting the regulation of redox homeostasis to amplify oxidative stress is of value in cancer therapy. However, therapeutic agents like nucleic acids, small molecular inhibitors, and chemotherapeutic drugs fail to exert effective cancer inhibition due to their low bioavailability, susceptibility to serum enzymes, and inefficiency in cell membrane penetrating. Therefore, specific delivery vectors are required to facilitate the intracellular delivery of anti-tumor drugs. In the past few decades, various engineered nanomaterials have been designed and developed for drug delivery. In particular, rational nanoparticles (NPs) have garnered more attention due to their splendid long circulation ability, modification capacity, and stimulation-responded release. In this review, the methods of ROS generation and ROS-regulated signaling in cancer development were firstly briefly introduced. The anti-oxidant system, including the metabolism shifting and anti-oxidant genes, were next reviewed, and the strategies of NPs-mediated targeted regulation of redox homeostasis were emphatically discussed. The main strategies include NPs-induced delivery of nucleic acids, small molecule inhibitors, chemotherapeutic agents, radiosensitizers, and NPs-induced ROS generation and GSH depletion. The future development of NP-mediated redox dyshomeostasis in cancer therapy and their challenges in clinical translation were finally discussed. Nanoparticles have been used to disrupt redox homeostasis for effective cancer therapy in various methods, mainly including targeting antioxidant systems, indirectly generating ROS and directly generating ROS as a ROS inducer. Abbreviation: PDT: photodynamic therapy; SDT: sonodynamic therapy; CDT: chemotherapy dynamic; RT: radiotherapy; CT: chemotherapy. • Redox homeostasis is protected in cancer cells to facilitate their development. • Anti-oxidant system is vital in redox homeostasis regulation. • Nanoparticles (NPs)-mediated targeted regulation of redox homeostasis can effectively inhibit cancer cells through multiple pathways. • NPs-mediated redox homeostasis targeting is potential in combinational cancer therapy.