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Recent progress of hypoxia-modulated multifunctional nanomedicines to enhance photodynamic therapy: opportunities,challenges, and future development

Institution:	1. Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, China;2. School of Pharmacy, Guangxi University of Chinese Medicine, Nanning 530200, China;3. Department of Pharmaceutics, the Second Hospital of Dalian Medical University, Dalian 116023, China

Abstract:	Hypoxia, a salient feature of most solid tumors, confers invasiveness and resistance to the tumor cells. Oxygen-consumption photodynamic therapy (PDT) suffers from the undesirable impediment of local hypoxia in tumors. Moreover, PDT could further worsen hypoxia. Therefore, developing effective strategies for manipulating hypoxia and improving the effectiveness of PDT has been a focus on antitumor treatment. In this review, the mechanism and relationship of tumor hypoxia and PDT are discussed. Moreover, we highlight recent trends in the field of nanomedicines to modulate hypoxia for enhancing PDT, such as oxygen supply systems, down-regulation of oxygen consumption and hypoxia utilization. Finally, the opportunities and challenges are put forward to facilitate the development and clinical transformation of PDT.

Keywords:	Hypoxia Photodynamic therapy Cancer Nanomedicine delivery systems Oxygen APCs"} {"#name":"keyword" "$":{"id":"kwrd0040"} "$$":[{"#name":"text" "_":"antigen-presenting cells AQ4N"} {"#name":"keyword" "$":{"id":"kwrd0050"} "$$":[{"#name":"text" "_":"banoxantrone Ce6"} {"#name":"keyword" "$":{"id":"kwrd0060"} "$$":[{"#name":"text" "_":"chlorin e6 calcium dioxide cerium oxide DC"} {"#name":"keyword" "$":{"id":"kwrd0090"} "$$":[{"#name":"text" "_":"dendritic cells DOX"} {"#name":"keyword" "$":{"id":"kwrd0100"} "$$":[{"#name":"text" "_":"doxorubicin DDS"} {"#name":"keyword" "$":{"id":"kwrd0110"} "$$":[{"#name":"text" "_":"drug delivery system EPR"} {"#name":"keyword" "$":{"id":"kwrd0120"} "$$":[{"#name":"text" "_":"enhanced permeability and retention FDA"} {"#name":"keyword" "$":{"id":"kwrd0130"} "$$":[{"#name":"text" "_":"U S Food and Drug Administration HIF"} {"#name":"keyword" "$":{"id":"kwrd0140"} "$$":[{"#name":"text" "_":"hypoxia-inducible factor hydrogen peroxide water Hb"} {"#name":"keyword" "$":{"id":"kwrd0180"} "$$":[{"#name":"text" "_":"hemoglobin HSA"} {"#name":"keyword" "$":{"id":"kwrd0190"} "$$":[{"#name":"text" "_":"human serum albumin MDSC"} {"#name":"keyword" "$":{"id":"kwrd0200"} "$$":[{"#name":"text" "_":"myeloid derived suppressive cells MDR1"} {"#name":"keyword" "$":{"id":"kwrd0210"} "$$":[{"#name":"text" "_":"multidrug resistance 1 manganese dioxide Mn-CDs"} {"#name":"keyword" "$":{"id":"kwrd0230"} "$$":[{"#name":"text" "_":"magnetofluorescent manganese-carbon dots MB"} {"#name":"keyword" "$":{"id":"kwrd0240"} "$$":[{"#name":"text" "_":"methylene blue NMR"} {"#name":"keyword" "$":{"id":"kwrd0250"} "$$":[{"#name":"text" "_":"nuclear magnetic resonance superoxide anion hydroxyl radical molecular oxygen PDT"} {"#name":"keyword" "$":{"id":"kwrd0290"} "$$":[{"#name":"text" "_":"photodynamic therapy PS"} {"#name":"keyword" "$":{"id":"kwrd0300"} "$$":[{"#name":"text" "_":"photosensitizers PFC"} {"#name":"keyword" "$":{"id":"kwrd0310"} "$$":[{"#name":"text" "_":"perfluorocarbon PFH"} {"#name":"keyword" "$":{"id":"kwrd0320"} "$$":[{"#name":"text" "_":"perfluoroethane ROS"} {"#name":"keyword" "$":{"id":"kwrd0330"} "$$":[{"#name":"text" "_":"reactive oxygen species RBCs"} {"#name":"keyword" "$":{"id":"kwrd0340"} "$$":[{"#name":"text" "_":"red blood cells TAM"} {"#name":"keyword" "$":{"id":"kwrd0350"} "$$":[{"#name":"text" "_":"tumor-associated macrophages TPZ"} {"#name":"keyword" "$":{"id":"kwrd0360"} "$$":[{"#name":"text" "_":"tirapazamine
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