title: Multifunctional gold nanostar conjugates for tumor imaging and combined photothermal and chemo-therapy.
abstract: Uniform gold nanostars (Au NS) were conjugated with cyclic RGD (cRGD) and near infrared (NIR) fluorescence probe (MPA) or anti-cancer drug (DOX) to obtain multi-functional nanoconstructs, Au-cRGD-MPA and Au-cRGD-DOX respectively. The NIR contrast agent Au-cRGD-MPA was shown to have low cytotoxicity. Using tumor cells and tumor bearing mice, these imaging nanoparticles demonstrated favorable tumor-targeting capability mediated by RGD peptide binding to its over-expressed receptor on the tumor cells. The multi-therapeutic analogue, Au-cRGD-DOX, integrates targeting tumor, chemotherapy and photo-thermotherapy into a single system. The synergistic effect of photo-thermal therapy and chemotherapy was demonstrated in different tumor cell lines and in vivo using S180 tumor-bearing mouse models. The viability of MDA-MB-231 cells was only 40 % after incubation with Au-cRGD-DOX and irradiation with NIR light. Both tail vein and intratumoral injections showed Au-cRGD-DOX treated mice exhibiting the slowest tumor increase. These results indicate that the multifunctional nanoconstruct is a promising combined therapeutic agent for tumor-targeting treatment, with the potential to enhance the anti-cancer treatment outcomes.
authors.affiliation: 1. Department of Biomedical Engineering, State Key Laboratory of Natural Medicines and School of Life Science and Technology, China Pharmaceutical University, 24 Tongjia Lane, Gulou District, Nanjing 210009, China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Chen
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.forename: Shuhang
authors.initials: S
authors.lastname: Dai
authors.forename: Yuxiang
authors.initials: Y
authors.lastname: Ma
authors.forename: Sisi
authors.initials: S
authors.lastname: Cui
authors.forename: Samuel
authors.initials: S
authors.lastname: Achilefu
authors.forename: Yueqing
authors.initials: Y
authors.lastname: Gu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics* / Q000494:pharmacology; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D004358:Drug Therapy / Q000379:methods*; D006046:Gold / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D006801:Humans; D051379:Mice; D049329:Nanostructures / Q000737:chemistry*; D009369:Neoplasms / Q000175:diagnosis* / Q000628:therapy*; D009842:Oligopeptides / Q000737:chemistry / Q000493:pharmacokinetics; D010648:Phenylacetates / Q000737:chemistry / Q000493:pharmacokinetics; D010778:Photochemotherapy / Q000379:methods*; D011971:Receptors, Immunologic / Q000378:metabolism; D018000:Receptors, Peptide / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D009842:Oligopeptides; D010648:Phenylacetates; D011971:Receptors, Immunologic; D018000:Receptors, Peptide; C051382:arginyl-glycyl-aspartic acid directed cell adhesion receptor; D006046:Gold; C047981:arginyl-glycyl-aspartic acid; D004317:Doxorubicin; C512803:alpha-methoxy-alpha-phenylacetic acid
keywords: RGD receptor; gold nanostar; near infrared imaging; photo-thermal therapy.; tumor-targeting
references.citation: Bioconjug Chem. 2012 Mar 21;23(3):586-95
references.pmid: 22369387
references.citation: Methods Enzymol. 1972;24:53-68
references.pmid: 4206745
references.citation: Small. 2010 Apr 9;6(7):811-7
references.pmid: 20225187
references.citation: Expert Opin Drug Deliv. 2010 May;7(5):577-87
references.pmid: 20345327
references.citation: Biomaterials. 2012 Oct;33(30):7519-29
references.pmid: 22809649
references.citation: Adv Mater. 2013 Jun 11;25(22):3055-61
references.pmid: 23404693
references.citation: Bioconjug Chem. 2010 Dec 15;21(12):2173-7
references.pmid: 21062090
references.citation: ACS Nano. 2011 Feb 22;5(2):1086-94
references.pmid: 21244012
references.citation: Small. 2011 Jan 17;7(2):169-83
references.pmid: 21213377
references.citation: Cytometry. 2002 Jan 1;47(1):24-31
references.pmid: 11774346
references.citation: ACS Nano. 2011 Jun 28;5(6):4319-28
references.pmid: 21609027
references.citation: Nat Biotechnol. 2013 Feb;31(2):148-53
references.pmid: 23292608
references.citation: J Am Chem Soc. 2012 Aug 1;134(30):12668-74
references.pmid: 22642558
references.citation: Nanomedicine (Lond). 2012 Dec;7(12):1791-4
references.pmid: 23249329
references.citation: Nat Rev Clin Oncol. 2012 Dec;9(12):688-99
references.pmid: 23165124
references.citation: Nat Nanotechnol. 2009 Nov;4(11):710-1
references.pmid: 19898521
references.citation: Med Oncol. 2013 Mar;30(1):322
references.pmid: 23254962
references.citation: Small. 2011 Jul 18;7(14):2052-60
references.pmid: 21688390
references.citation: Nat Biotechnol. 2001 Apr;19(4):316-7
references.pmid: 11283581
references.citation: Clin Cancer Res. 2009 Feb 1;15(3):876-86
references.pmid: 19188158
references.citation: ACS Nano. 2012 Apr 24;6(4):3318-26
references.pmid: 22424173
references.citation: Am J Pathol. 1998 Nov;153(5):1347-51
references.pmid: 9811323
references.citation: Small. 2012 Mar 12;8(5):746-53
references.pmid: 22271594
references.citation: Nanomedicine. 2012 Nov;8(8):1355-63
references.pmid: 22370335
references.citation: Angew Chem Int Ed Engl. 2011 Aug 8;50(33):7581-6
references.pmid: 21721086
references.citation: Nano Lett. 2010 Oct 13;10(10):3816-22
references.pmid: 20853888
references.citation: Nano Lett. 2008 May;8(5):1492-500
references.pmid: 18412402
references.citation: Nano Lett. 2007 Mar;7(3):729-32
references.pmid: 17279802
references.citation: ACS Nano. 2011 Mar 22;5(3):1995-2003
references.pmid: 21344891
references.citation: ACS Nano. 2010 Oct 26;4(10):5887-96
references.pmid: 20863096
references.citation: Theranostics. 2012;2(8):757-68
references.pmid: 22916075
references.citation: Nano Lett. 2005 Apr;5(4):585-9
references.pmid: 15826091
references.citation: Lasers Med Sci. 2008 Jul;23(3):217-28
references.pmid: 17674122
references.citation: J Am Chem Soc. 2012 Jul 18;134(28):11358-61
references.pmid: 22734608
references.citation: Int J Nanomedicine. 2012;7:915-24
references.pmid: 22412298