title: Hypoxia-responsive polymeric nanoparticles for tumor-targeted drug delivery.
abstract: Hypoxia is a condition found in various intractable diseases. Here, we report self-assembled nanoparticles which can selectively release the hydrophobic agents under hypoxic conditions. For the preparation of hypoxia-responsive nanoparticles (HR-NPs), a hydrophobically modified 2-nitroimidazole derivative was conjugated to the backbone of the carboxymethyl dextran (CM-Dex). Doxorubicin (DOX), a model drug, was effectively encapsulated into the HR-NPs. The HR-NPs released DOX in a sustained manner under the normoxic condition (physiological condition), whereas the drug release rate remarkably increased under the hypoxic condition. From in vitro cytotoxicity tests, it was found the DOX-loaded HR-NPs showed higher toxicity to hypoxic cells than to normoxic cells. Microscopic observation showed that the HR-NPs could effectively deliver DOX into SCC7 cells under hypoxic conditions. In vivo biodistribution study demonstrated that HR-NPs were selectively accumulated at the hypoxic tumor tissues. As consequence, drug-loaded HR-NPs exhibited high anti-tumor activity in vivo. Overall, the HR-NPs might have a potential as nanocarriers for drug delivery to treat hypoxia-associated diseases.
authors.affiliation: Department of Polymer Science and Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea; School of Chemical Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Thavasyappan
authors.initials: T
authors.lastname: Thambi
authors.affiliation: Department of Polymer Science and Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea; School of Chemical Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: V G
authors.initials: VG
authors.lastname: Deepagan
authors.affiliation: Department of Polymer Science and Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea; School of Chemical Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea; Biomedical Research Institute, Korea Institute of Science and Technology, Seoul 136-791, Republic of Korea.
authors.forename: Hong Yeol
authors.initials: HY
authors.lastname: Yoon
authors.affiliation: Department of Polymer Science and Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea; School of Chemical Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Hwa Seung
authors.initials: HS
authors.lastname: Han
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Seol-Hee
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Polymer Science and Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea; Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Soyoung
authors.initials: S
authors.lastname: Son
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea; Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Dong-Gyu
authors.initials: DG
authors.lastname: Jo
authors.affiliation: Department of Materials Science and Engineering, Seoul National University, Seoul 151-744, Republic of Korea.
authors.forename: Cheol-Hee
authors.initials: CH
authors.lastname: Ahn
authors.affiliation: School of Chemical Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea; NanoBio Fusion Research Center, Korea Research Institute of Chemical Technology, Daejeon 305-600, Republic of Korea.
authors.forename: Yung Doug
authors.initials: YD
authors.lastname: Suh
authors.affiliation: Biomedical Research Institute, Korea Institute of Science and Technology, Seoul 136-791, Republic of Korea.
authors.forename: Kwangmeyung
authors.initials: K
authors.lastname: Kim
authors.affiliation: Biomedical Research Institute, Korea Institute of Science and Technology, Seoul 136-791, Republic of Korea.
authors.forename: Ick Chan
authors.initials: IC
authors.lastname: Kwon
authors.affiliation: Department of Polymer Science and Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea; School of Chemical Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Doo Sung
authors.initials: DS
authors.lastname: Lee
authors.affiliation: Department of Polymer Science and Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea; School of Chemical Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea; NanoBio Fusion Research Center, Korea Research Institute of Chemical Technology, Daejeon 305-600, Republic of Korea; Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Suwon 440-746, Republic of Korea. Electronic address: biopol@gmail.com.
authors.forename: Jae Hyung
authors.initials: JH
authors.lastname: Park
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000627:therapeutic use; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000008:administration & dosage* / Q000627:therapeutic use; D016503:Drug Delivery Systems; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D051379:Mice; D053758:Nanoparticles; D009369:Neoplasms / Q000188:drug therapy*; D011108:Polymers / Q000737:chemistry*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000903:Antibiotics, Antineoplastic; D011108:Polymers; D004317:Doxorubicin
keywords: 2-Nitroimidazole; Bioreduction; Drug delivery; Hypoxia; Nanoparticles