title: Specific targeting of A54 homing peptide-functionalized dextran-g-poly(lactic-co-glycolic acid) micelles to tumor cells.
abstract: The delivery of chemotherapeutics into tumor cells is a fundamental knot for tumor-target therapy to improve the curative effect and avoid side effects. Here, A54 peptide-functionalized poly(lactic-co-glycolic acid)-grafted dextran (A54-Dex-PLGA) was synthesized. The synthesized A54-Dex-PLGA self-assembled to form micelles with a low critical micelle concentration of 16.79 μg·mL(-1) and diameter of about 50 nm. With doxorubicin (DOX) base as a model antitumor drug, the drug-encapsulation efficiency of DOX-loaded A54-Dex-PLGA micelles (A54-Dex-PLGA/DOX) reached up to 75%. In vitro DOX release from the A54-Dex-PLGA/DOX was prolonged to 72 hours. The A54-Dex-PLGA micelles presented excellent internalization ability into hepatoma cells (BEL-7402 cell line and HepG2 cell line) in vitro, and the cellular uptake of the micelles by the BEL-7402 cell line was specific, which was demonstrated by the blocking experiment. In vitro antitumor activity studies confirmed that A54-Dex-PLGA/DOX micelles suppressed tumor-cell (BEL-7402 cell) growth more effectively than Dex-PLGA micelles. Furthermore, in vivo biodistribution testing demonstrated that the A54-Dex-PLGA micelles had a higher distribution ability to BEL-7402 tumors than that to HepG2 tumors.
authors: College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, People's Republic of China.
authors: Jun-Qing
authors: JQ
authors: Situ
authors: Women's Hospital, Zhejiang University, Hangzhou, People's Republic of China.
authors: Yi-Qing
authors: YQ
authors: Ye
authors: Department of Radiology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China.
authors: Xiu-Liang
authors: XL
authors: Zhu
authors: Department of Radiology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China.
authors: Ri-Sheng
authors: RS
authors: Yu
authors: College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, People's Republic of China.
authors: Jian
authors: J
authors: You
authors: College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, People's Republic of China.
authors: Hong
authors: H
authors: Yuan
authors: College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, People's Republic of China.
authors: Fu-Qiang
authors: FQ
authors: Hu
authors: College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, People's Republic of China.
authors: Yong-Zhong
authors: YZ
authors: Du
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003911:Dextrans / Q000737:chemistry / Q000493:pharmacokinetics; D004317:Doxorubicin / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D016503:Drug Delivery Systems; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry / Q000493:pharmacokinetics; D008823:Micelles; D011100:Polyglycolic Acid / Q000737:chemistry / Q000493:pharmacokinetics; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D014018:Tissue Distribution
chemical_list: D000970:Antineoplastic Agents; D003911:Dextrans; D008823:Micelles; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D004317:Doxorubicin
keywords: doxorubicin; homing peptide; polymeric micelles; tumor-cell targeting
references: ACS Nano. 2013 Oct 22;7(10):8583-92
references: 24028526
references: Expert Opin Pharmacother. 2007 Jun;8(8):1039-58
references: 17516870
references: J Pharm Sci. 2009 Jun;98(6):2104-12
references: 18823029
references: Cancer Res. 1986 Dec;46(12 Pt 1):6387-92
references: 2946403
references: Cancer Sci. 2009 Apr;100(4):572-9
references: 19462526
references: J Pharm Sci. 2003 Jul;92(7):1343-55
references: 12820139
references: Biomaterials. 2012 Dec;33(34):8858-67
references: 22959183
references: Mol Cancer Res. 2010 Feb;8(2):135-44
references: 20145035
references: Mol Pharmacol. 1994 Apr;45(4):649-56
references: 8183243
references: J Nanosci Nanotechnol. 2014 Jan;14(1):98-114
references: 24730253
references: J Pharm Sci. 2013 Jan;102(1):145-53
references: 23132353
references: Science. 2002 Aug 9;297(5583):967-73
references: 12169723
references: ACS Nano. 2010 Nov 23;4(11):6894-902
references: 20939508
references: Mol Biosyst. 2011 Jun;7(6):2040-7
references: 21491031
references: Eur J Pharm Biopharm. 2014 May;87(1):152-9
references: 24361535
references: Eur J Pharm Biopharm. 2009 Mar;71(3):409-19
references: 19070661
references: J Control Release. 2014 Feb 10;175:48-53
references: 24345789
references: Pharmaceutics. 2013 Mar 22;5(1):201-19
references: 24300405
references: J Mater Sci Mater Med. 2009 Jan;20(1):301-7
references: 18791664
references: J Control Release. 2002 Jul 18;82(1):17-27
references: 12106973
references: Nature. 1996 Mar 28;380(6572):364-6
references: 8598934
references: Curr Opin Chem Biol. 2002 Jun;6(3):399-404
references: 12023122
references: Biomaterials. 2008 May;29(15):2408-14
references: 18295328
references: Biopolymers. 2002;66(3):184-99
references: 12385037
references: Cancer. 2012 Apr 1;118(7):1919-24
references: 21882180
references: Int J Nanomedicine. 2013;8:1551-62
references: 23637528
references: Mol Pharm. 2008 Jul-Aug;5(4):496-504
references: 18611037
references: J Biomed Mater Res A. 2008 Jan;84(1):10-8
references: 17600321
references: Biomaterials. 2013 Jun;34(18):4510-9
references: 23510855
references: J Mater Sci Mater Med. 2010 Feb;21(2):665-74
references: 19834788
references: Int J Nanomedicine. 2011;6:1415-27
references: 21796244
references: Arch Pharm Res. 2006 Aug;29(8):712-9
references: 16964768