title: Tumor-targeting peptide conjugated pH-responsive micelles as a potential drug carrier for cancer therapy.
abstract: Herein, we prepared tumor-targeting peptide (AP peptide; CRKRLDRN) conjugated pH-responsive polymeric micelles (pH-PMs) in cancer therapy by active and pH-responsive tumor targeting delivery systems, simultaneously. The active tumor targeting and tumoral pH-responsive polymeric micelles were prepared by mixing AP peptide conjugated PEG-poly(d,l-lactic acid) block copolymer (AP-PEG-PLA) into the pH-responsive micelles of methyl ether poly(ethylene glycol) (MPEG)-poly(beta-amino ester) (PAE) block copolymer (MPEG-PAE). These mixed amphiphilic block copolymers were self-assembled to form stable AP peptide-conjugated and pH-responsive AP-PEG-PLA/MPEG-PAE micelles (AP-pH-PMs) with an average size of 150 nm. The AP-pH-PMs containing 10 wt % of AP-PEG-PLA showed a sharp pH-dependent micellization/demicellization transition at the tumoral acid pH. Also, they presented the pH-dependent drug release profile at the acidic pH of 6.4. The fluorescence dye, TRITC, encapsulated AP-pH-PMs (TRITC-AP-pH-PMs) presented the higher tumor-specific targeting ability in vitro cancer cell culture system and in vivo tumor-bearing mice, compared to control pH-responsive micelles of MPEG-PAE. For the cancer therapy, the anticancer drug, doxorubicin (DOX), was efficiently encapsulated into the AP-pH-PMs (DOX-AP-pH-PMs) with a higher loading efficiency. DOX-AP-pH-PMs efficiently deliver anticancer drugs in MDA-MB231 human breast tumor-bearing mice, resulted in excellent anticancer therapeutic efficacy, compared to free DOX and DOX encapsulated MEG-PAE micelles, indicating the excellent tumor targeting ability of AP-pH-PMs. Therefore, these tumor-targeting peptide-conjugated and pH-responsive polymeric micelles have great potential application in cancer therapy.
authors.affiliation: Department of Polymer Science and Engineering, Sungkyunkwan University, Suwon, 440-746, Republic of Korea.
authors.forename: Xiang Lan
authors.initials: XL
authors.lastname: Wu
authors.forename: Jong Ho
authors.initials: JH
authors.lastname: Kim
authors.forename: Heebeom
authors.initials: H
authors.lastname: Koo
authors.forename: Sang Mun
authors.initials: SM
authors.lastname: Bae
authors.forename: Hyeri
authors.initials: H
authors.lastname: Shin
authors.forename: Min Sang
authors.initials: MS
authors.lastname: Kim
authors.forename: Byung-Heon
authors.initials: BH
authors.lastname: Lee
authors.forename: Rang-Woon
authors.initials: RW
authors.lastname: Park
authors.forename: In-San
authors.initials: IS
authors.lastname: Kim
authors.forename: Kuiwon
authors.initials: K
authors.lastname: Choi
authors.forename: Ick Chan
authors.initials: IC
authors.lastname: Kwon
authors.forename: Kwangmeyung
authors.initials: K
authors.lastname: Kim
authors.forename: Doo Sung
authors.initials: DS
authors.lastname: Lee
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D004337:Drug Carriers / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics; D006801:Humans; D006863:Hydrogen-Ion Concentration; D051379:Mice; D008823:Micelles; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D009842:Oligopeptides / Q000737:chemistry* / Q000378:metabolism; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D008823:Micelles; D009842:Oligopeptides; D011108:Polymers; C507253:poly(beta-amino ester); D011092:Polyethylene Glycols; D004317:Doxorubicin; C028210:monomethoxypolyethylene glycol