title: Tumor microenvironment-specific nanoparticles activatable by stepwise transformation.
abstract: In an attempt to develop the tumor-targeted nanocarrier which can surmount major challenges for in vivo application, we prepared tumor microenvironment-specific nanoparticles which can be sequentially activated at the extracellular and intracellular levels of tumor tissue by stepwise transformation. This polymeric nanoparticle has been prepared using an amphiphilic polyethyleneimine derivative with the pH-responsive charge-convertible moiety and the reduction-responsive crosslink. Once reaching the tumor tissue in vivo after systemic administration, the surface charge of this nanoparticle can be converted from negative to positive by recognizing the mildly acidic extracellular matrix of tumor, allowing for the enhanced cellular uptake. After the cellular uptake, the nanoparticle can selectively release the drug at the intracellular level since it has the chemically crosslinked core by the disulfide bond which is cleaved in intracellular reductive environment. The tumor microenvironment-specific nanoparticle shows the high tumor targetability and dramatically improves the antitumor efficacy of the drug.
authors.affiliation: Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology (SAIHST), Sungkyunkwan University, 2066, Seobu-ro, Jangan-gu, Suwon 440-746, Republic of Korea.
authors.forename: Hyewon
authors.initials: H
authors.lastname: Ko
authors.affiliation: Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology (SAIHST), Sungkyunkwan University, 2066, Seobu-ro, Jangan-gu, Suwon 440-746, Republic of Korea.
authors.forename: Soyoung
authors.initials: S
authors.lastname: Son
authors.affiliation: School of Chemical Engineering, College of Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Jueun
authors.initials: J
authors.lastname: Jeon
authors.affiliation: School of Chemical Engineering, College of Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Thavasyappan
authors.initials: T
authors.lastname: Thambi
authors.affiliation: School of Chemical Engineering, College of Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Seunglee
authors.initials: S
authors.lastname: Kwon
authors.affiliation: School of Medicine, Kyungpook National University, 680, Gukchaebosang-ro, Jung-gu, Daegu 700-842, Republic of Korea.
authors.forename: Yee Soo
authors.initials: YS
authors.lastname: Chae
authors.affiliation: School of Medicine, Kyungpook National University, 680, Gukchaebosang-ro, Jung-gu, Daegu 700-842, Republic of Korea.
authors.forename: Young Mo
authors.initials: YM
authors.lastname: Kang
authors.affiliation: Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology (SAIHST), Sungkyunkwan University, 2066, Seobu-ro, Jangan-gu, Suwon 440-746, Republic of Korea; School of Chemical Engineering, College of Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea. Electronic address: jhpark1@skku.edu.
authors.forename: Jae Hyung
authors.initials: JH
authors.lastname: Park
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D004317:Doxorubicin / Q000008:administration & dosage* / Q000627:therapeutic use; D004337:Drug Carriers / Q000737:chemistry*; D065546:Drug Liberation; D006801:Humans; D006863:Hydrogen-Ion Concentration; D061986:MCF-7 Cells; D053758:Nanoparticles / Q000737:chemistry*; D011094:Polyethyleneimine / Q000737:chemistry*; D013499:Surface Properties; D059016:Tumor Microenvironment / Q000187:drug effects*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D004317:Doxorubicin; D011094:Polyethyleneimine
keywords: Biostability; Drug delivery; Stepwise transformation; Tumor microenvironment