title: The efficiency of tumor-specific pH-responsive peptide-modified polymeric micelles containing paclitaxel.
abstract: The acidic pH in tumor tissues could be used for targeting solid tumors. In the present study, we designed a tumor-specific pH-responsive peptide H(7)K(R(2))(2), which could respond to the acidic pH in tumor tissues, and prepared H(7)K(R(2))(2)-modified polymeric micelles containing paclitaxel (PTX-PM-H(7)K(R(2))(2)) in order to evaluate their potential targeting of tumor cells and tumor endothelial cells and their anti-tumor activity in mice with tumor cells. PTX-PM-H(7)K(R(2))(2) was prepared by a thin-film hydration method. The in vitro release of PTX from PTX-PM-H(7)K(R(2))(2) was tested. The in vitro targeting characteristics of H(7)K(R(2))(2)-modified polymeric micelles on HUVEC (human umbilical vein endothelial cells) and MCF-7 (human breast adenocarcinoma cells) were evaluated. The in vivo targeting activity of H(7)K(R(2))(2)-modified polymeric micelles and the in vivo anti-tumor activity of PTX-PM-H(7)K(R(2))(2) were also investigated in MCF-7 tumor-bearing mice. The released PTX from the PTX-PM-H(7)K(R(2))(2) was not affected by the pH. The targeting activity of the H(7)K(R(2))(2)-modified polymeric micelles was demonstrated by in vitro flow cytometry and confocal microscopy as well as in vivo biodistribution. PTX-PM-H(7)K(R(2))(2) produced very marked anti-tumor and anti-angiogenic activity in MCF-7 tumor-bearing mice in vivo.
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Xueyuan road, 38, Beijing 100191, China.
authors.forename: Bing-Xiang
authors.initials: BX
authors.lastname: Zhao
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhao
authors.forename: Yue
authors.initials: Y
authors.lastname: Huang
authors.forename: Lin-Min
authors.initials: LM
authors.lastname: Luo
authors.forename: Ping
authors.initials: P
authors.lastname: Song
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.forename: Su
authors.initials: S
authors.lastname: Chen
authors.forename: Ke-Fu
authors.initials: KF
authors.lastname: Yu
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002232:Carbocyanines / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008823:Micelles; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D055806:Microvessels / Q000187:drug effects / Q000473:pathology; D009369:Neoplasms / Q000098:blood supply / Q000473:pathology*; D009389:Neovascularization, Pathologic / Q000473:pathology; D017239:Paclitaxel / Q000737:chemistry / Q000494:pharmacology*; D010316:Particle Size; D010455:Peptides / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D014018:Tissue Distribution / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D002232:Carbocyanines; D008823:Micelles; D010455:Peptides; D011108:Polymers; D017239:Paclitaxel