title: Single peptide ligand-functionalized uniform hollow mesoporous silica nanoparticles achieving dual-targeting drug delivery to tumor cells and angiogenic blood vessel cells.
abstract: BACKGROUND
  The purpose of this study was to construct hollow mesoporous silica nanoparticles (HMSN) decorated with tLyp-1 peptide (tHMSN) for dual-targeting drug delivery to tumor cells and angiogenic blood vessel cells.
  
  
  METHODS
  HMSN were synthesized de novo using a novel cationic surfactant-assisted selective etching strategy and were then modified with tLyp-1. Multiple methods, including transmission electron microscopy, X-ray photoelectron spectroscopy, thermogravimetric analysis, bicinchoninic acid assay, and nitrogen adsorption and desorption isotherms, were used to characterize the tHMSN. Doxorubicin were chosen as the model cargo, and the uptake of doxorubicin-loaded tHMSN into MDA-MB-231 cells and human umbilical vein endothelial cells (HUVECs), as models of tumor cells and tumor neovascular endothelial cells, respectively, were observed and detected by confocal laser scanning microscopy and flow cytometry. An in vitro pharmacodynamic study and a study of the mechanism via which the nanoparticles were endocytosed were also performed.
  
  
  RESULTS
  HMSN with a highly uniform size and well oriented mesopores were synthesized. After tHMSN were characterized, enhanced uptake of the cargo carried by tHMSN into MDA-MB-231 cells and HUVECs compared with that of their unmodified counterparts was validated by confocal laser scanning microscopy and flow cytometry at the qualitative and quantitative levels, respectively. Further, the pharmacodynamic study suggested that, compared with their unmodified counterparts, doxorubicin-loaded tHMSN had an enhanced inhibitory effect on MDA-MB-231 cells and HUVECs in vitro. Finally, a preliminary study on the mechanism by which the nanoparticles were endocytosed indicated that the clathrin-mediated endocytosis pathway has a primary role in the transport of tHMSN into the cytoplasm.
  
  
  CONCLUSIONS
  tHMSN might serve as an effective active targeting nanocarrier strategy for anti-mammary cancer drug delivery.
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, People's Republic of China ; Department of Pharmacy, Bengbu Medical College, Bengbu, People's Republic of China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, People's Republic of China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Chen
authors.affiliation: College of Pharmaceutical Science, Soochow University, Suzhou, People's Republic of China.
authors.forename: Ming
authors.initials: M
authors.lastname: Xu
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, People's Republic of China.
authors.forename: Guannan
authors.initials: G
authors.lastname: Guan
authors.affiliation: College of Pharmaceutical Science, Soochow University, Suzhou, People's Republic of China.
authors.forename: Wen
authors.initials: W
authors.lastname: Hu
authors.affiliation: Department of Pharmacy, Bengbu Medical College, Bengbu, People's Republic of China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liang
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, People's Republic of China.
authors.forename: Xiuli
authors.initials: X
authors.lastname: Zhao
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, People's Republic of China.
authors.forename: Mingxi
authors.initials: M
authors.lastname: Qiao
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, People's Republic of China.
authors.forename: Dawei
authors.initials: D
authors.lastname: Chen
authors.affiliation: Department of Pharmacy, Bengbu Medical College, Bengbu, People's Republic of China.
authors.forename: Hao
authors.initials: H
authors.lastname: Liu
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage; D045744:Cell Line, Tumor / Q000187:drug effects; D003020:Clothing; D004317:Doxorubicin / Q000008:administration & dosage / Q000737:chemistry; D004337:Drug Carriers / Q000008:administration & dosage / Q000493:pharmacokinetics; D016503:Drug Delivery Systems / Q000379:methods*; D004705:Endocytosis; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects; D006801:Humans; D008024:Ligands; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry* / Q000633:toxicity; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000473:pathology; D010455:Peptides / Q000737:chemistry*; D056951:Photoelectron Spectroscopy; D012822:Silicon Dioxide / Q000737:chemistry; D013818:Thermogravimetry
chemical_list: D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D008024:Ligands; D010455:Peptides; D012822:Silicon Dioxide; D004317:Doxorubicin
keywords: anti-mammary cancer; drug delivery; hollow mesoporous silica nanoparticles; tLyp-1 peptide
references.citation: Cell. 1998 Mar 20;92(6):735-45
references.pmid: 9529250
references.citation: Cancer Cell. 2009 Mar 3;15(3):232-9
references.pmid: 19249681
references.citation: Nat Med. 2013 Nov;19(11):1423-37
references.pmid: 24202395
references.citation: ACS Nano. 2010 Jan 26;4(1):529-39
references.pmid: 20041633
references.citation: Toxicol In Vitro. 2009 Jun;23(4):697-703
references.pmid: 19254755
references.citation: Chem Res Toxicol. 2007 Dec;20(12):1913-8
references.pmid: 17990852
references.citation: Nano Lett. 2008 Sep;8(9):2867-71
references.pmid: 18698725
references.citation: Mol Pharm. 2011 Dec 5;8(6):1996-2011
references.pmid: 21770407
references.citation: Angew Chem Int Ed Engl. 2008;47(31):5806-11
references.pmid: 18574831
references.citation: Nat Rev Mol Cell Biol. 2006 Jun;7(6):404-14
references.pmid: 16723976
references.citation: Cancer Res. 2006 Oct 15;66(20):10073-82
references.pmid: 17047071
references.citation: Biomaterials. 2013 Apr;34(12):3150-8
references.pmid: 23369218
references.citation: Cell. 2011 Oct 14;147(2):275-92
references.pmid: 22000009
references.citation: Mol Pharm. 2014 Mar 3;11(3):1042-52
references.pmid: 24521297
references.citation: Nanoscale. 2011 Apr;3(4):1632-9
references.pmid: 21305093
references.citation: Biomaterials. 2014 Feb;35(7):2374-82
references.pmid: 24342723
references.citation: Adv Mater. 2014 Jan 22;26(3):391-411
references.pmid: 24142549
references.citation: Biomaterials. 2014 Jan;35(1):316-26
references.pmid: 24125776
references.citation: Nanoscale. 2013 Mar 21;5(6):2205-18
references.pmid: 23400270
references.citation: Clin Cancer Res. 2008 Dec 15;14(24):8052-60
references.pmid: 19088020
references.citation: Cancer Cell. 2007 Jan;11(1):53-67
references.pmid: 17222790
references.citation: Oncogene. 2012 Aug 16;31(33):3754-63
references.pmid: 22179825
references.citation: Cancer Cell. 2009 Mar 3;15(3):220-31
references.pmid: 19249680
references.citation: Small. 2009 Dec;5(23):2722-9
references.pmid: 19780070
references.citation: Biomaterials. 2013 Apr;34(11):2719-30
references.pmid: 23337327
references.citation: Cancer Res. 2013 Jan 15;73(2):804-12
references.pmid: 23151901
references.citation: Adv Mater. 2014 Oct 22;26(39):6742-8
references.pmid: 25159109
references.citation: Small. 2012 Dec 21;8(24):3816-22
references.pmid: 22903778
references.citation: Biomaterials. 2014 May;35(14):4319-32
references.pmid: 24565520
references.citation: J Biol Chem. 2003 Dec 5;278(49):48848-60
references.pmid: 14514674
references.citation: Chem Soc Rev. 2013 May 7;42(9):3862-75
references.pmid: 23403864
references.citation: Small. 2011 Jan 17;7(2):271-80
references.pmid: 21213393
references.citation: Adv Drug Deliv Rev. 2013 May;65(5):689-702
references.pmid: 22921598
references.citation: Adv Mater. 2011 Mar 25;23(12):H84-9
references.pmid: 21360776
references.citation: Cancer Res. 2001 Aug 1;61(15):5736-40
references.pmid: 11479209
references.citation: ACS Nano. 2013 Nov 26;7(11):9512-7
references.pmid: 24215340
references.citation: Blood. 2005 Mar 1;105(5):1992-9
references.pmid: 15522955
references.citation: Biomaterials. 2013 Jan;34(4):1135-45
references.pmid: 23146434
references.citation: Science. 1998 Jan 16;279(5349):377-80
references.pmid: 9430587
references.citation: Adv Mater. 2010 Apr 6;22(13):1516-20
references.pmid: 20437501
references.citation: Nat Rev Clin Oncol. 2011 Apr;8(4):210-21
references.pmid: 21364524
references.citation: J Control Release. 2011 Jul 30;153(2):141-8
references.pmid: 21447361
references.citation: Biomaterials. 2013 Jul;34(22):5640-50
references.pmid: 23639530
references.citation: ACS Nano. 2013 Feb 26;7(2):994-1005
references.pmid: 23289892