title: In vitro and in vivo evaluation of APRPG-modified angiogenic vessel targeting micelles for anticancer therapy.
abstract: The study was aimed to evaluate the antitumor potential of the Ala-Pro-Arg-Pro-Gly (APRPG)-modified angiogenic vessel targeting drug delivery system using paclitaxel (PTX) as a model drug. In this study, an angiogenesis homing peptide APRPG was conjugated to the amphipathic copolymer PLGA-PEG and the synthesized copolymer APRPG-PEG-PLGA was used to prepare PTX encapsulated micelles (APRPG-PEG-Mic). The micelles were uniform spherical and exhibited a unimodal particle size distribution and a slight negative zeta-potential. The in vitro drug release result demonstrated a significant sustained release property of APRPG-PEG-Mic. Compared to Taxol(®) and Cont-PEG-Mic, APRPG-PEG-Mic showed a stronger cytotoxicity against two cancerous cell lines. In the cell uptake studies, the APRPG-modified micelles enhanced intracellular fluorescent intensity in EA.hy926 cells. The biodistribution study revealed the accumulation of APRPG-PEG-Mic in tumor tissues as a result of passive accumulation and active targeting. In comparison with Taxol(®) and Cont-PEG-Mic, APRPG-PEG-Mic reduced the tumor volume more significantly and prolonged the survival time of tumor-bearing mice, indicating a higher antitumor efficacy and lower systematic side effects of APRPG-PEG-Mic. The results indicated that APRPG-modified micelles could be an efficient target-delivery method to angiogenic vessels and a highly promising therapeutic system in anticancer therapy.
authors.affiliation: Department of Pharmaceutics, Shenyang Pharmaceutical University, 103 Wenhua Road, 110016 Shenyang, China.
authors.forename: Pan
authors.initials: P
authors.lastname: Guo
authors.affiliation: Department of Pharmaceutics, Shenyang Pharmaceutical University, 103 Wenhua Road, 110016 Shenyang, China.
authors.forename: Shuangshuang
authors.initials: S
authors.lastname: Song
authors.affiliation: Department of Pharmaceutics, Shenyang Pharmaceutical University, 103 Wenhua Road, 110016 Shenyang, China.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Pharmaceutics, Shenyang Pharmaceutical University, 103 Wenhua Road, 110016 Shenyang, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Department of Pharmaceutics, Shenyang Pharmaceutical University, 103 Wenhua Road, 110016 Shenyang, China.
authors.forename: Jiatong
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Department of Pharmaceutics, Shenyang Pharmaceutical University, 103 Wenhua Road, 110016 Shenyang, China.
authors.forename: Xinggang
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Pharmaceutics, Shenyang Pharmaceutical University, 103 Wenhua Road, 110016 Shenyang, China. Electronic address: spu_pws@163.com.
authors.forename: Weisan
authors.initials: W
authors.lastname: Pan
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D001692:Biological Transport; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D016503:Drug Delivery Systems; D065546:Drug Liberation; D006801:Humans; D008297:Male; D051379:Mice; D008823:Micelles; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D009842:Oligopeptides / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D017239:Paclitaxel / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D011092:Polyethylene Glycols / Q000737:chemistry; D011098:Polyglactin 910 / Q000737:chemistry; D014018:Tissue Distribution; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D008823:Micelles; D009842:Oligopeptides; C490869:alanyl-prolyl-arginyl-prolyl-glycine; C102418:poly(lactic-glycolic acid)-poly(ethyleneglycol) copolymer; D011098:Polyglactin 910; D011092:Polyethylene Glycols; D017239:Paclitaxel
keywords: Angiogenic vessel targeting; Anticancer therapy; Long circulation; Micelle; Paclitaxel; Tumor targeting