title: Modulating tumor hypoxia by nanomedicine for effective cancer therapy.
abstract: Hypoxia, a characteristic feature of tumors, is indispensable to tumor angiogenesis, metastasis, and multi drug resistance. Hypoxic avascular regions, deeply embedded inside the tumors significantly hinder delivery of therapeutic agents. The low oxygen tension results in resistance to the current applied anti-cancer therapeutics including radiotherapy, chemotherapy, and photodynamic therapy, the efficacy of which is firmly tied to the level of tumor oxygen supply. However, emerging data indicate that nanocarriers/nanodrugs can offer substantial benefits to improve the efficacy of current therapeutics, through modulation of tumor hypoxia. This review aims to introduce the most recent advances made in nanocarrier mediated targeting of tumor hypoxia. The first part is dedicated to the approaches by which nanocarriers could be designed to target/leverage hypoxia. These approaches include i) inhibiting Hypoxia Inducer Factor (HIF-1α); ii) hypoxia activated prodrugs/linkers; and iii) obligate anaerobe mediated targeting of tumor hypoxia. The second part, details novel nanosystems proposed to modulate tumor hypoxia through tumor oxygenation. These methods seek to lessen tumor hypoxia through vascular normalization, or reoxygenation therapy. The reoxygenation of tumor could be accomplished by: i) generation of oxygen filled nanocarriers; ii) natural/artificial oxygen nanocarriers; and iii) oxygen generators. The efficacy of each approach and their potential in cancer therapy is further discussed.
authors.affiliation: Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.|Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Rana
authors.initials: R
authors.lastname: Jahanban-Esfahlan
authors.affiliation: Department of Analytical Chemistry, University of Valencia, Valencia, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: de la Guardia
authors.affiliation: Students Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Delshad
authors.initials: D
authors.lastname: Ahmadi
authors.affiliation: Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.|Molecular Targeting Therapy Research Group, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.|Department of Clinical Biochemistry and Laboratory Medicine, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Bahman
authors.identifier: http://orcid.org/0000-0002-4220-1527
authors.initials: B
authors.lastname: Yousefi
mesh_terms: D015687:Cell Hypoxia / Q000187:drug effects*; D004337:Drug Carriers / Q000627:therapeutic use*; D006801:Humans; D050997:Nanomedicine; D049329:Nanostructures / Q000627:therapeutic use*; D009369:Neoplasms / Q000473:pathology / Q000628:therapy*; D009389:Neovascularization, Pathologic / Q000473:pathology; D010100:Oxygen / Q000378:metabolism / Q000627:therapeutic use*; D000072258:Tumor Hypoxia / Q000187:drug effects*
chemical_list: D004337:Drug Carriers; D010100:Oxygen
keywords: cancer; chemotherapy; hypoxia; nanocarriers; nanomedicine