title: A specifically designed nanoconstruct associates, internalizes, traffics in cardiovascular cells, and accumulates in failing myocardium: a new strategy for heart failure diagnostics and therapeutics.
abstract: OBJECTIVE
  Ongoing inflammation and endothelial dysfunction occurs within the local microenvironment of heart failure, creating an appropriate scenario for successful use and delivery of nanovectors. This study sought to investigate whether cardiovascular cells associate, internalize, and traffic a nanoplatform called mesoporous silicon vector (MSV), and determine its intravenous accumulation in cardiac tissue in a murine model of heart failure.
  
  
  RESULTS
  In vitro cellular uptake and intracellular trafficking of MSVs was examined by scanning electron microscopy, confocal microscopy, time-lapse microscopy, and flow cytometry in cardiac myocytes, fibroblasts, smooth muscle cells, and endothelial cells. The MSVs were internalized within the first hours, and trafficked to perinuclear regions in all the cell lines. Cytotoxicity was investigated by annexin V and cell cycle assays. No significant evidence of toxicity was found. In vivo intravenous cardiac accumulation of MSVs was examined by high content fluorescence and confocal microscopy, with results showing increased accumulation of particles in failing hearts compared with normal hearts. Similar to observations in vitro, MSVs were able to associate, internalize, and traffic to the perinuclear region of cardiomyocytes in vivo.
  
  
  CONCLUSIONS
  Results show that MSVs associate, internalize, and traffic in cardiovascular cells without any significant toxicity. Furthermore, MSVs accumulate in failing myocardium after intravenous administration, reaching intracellular regions of the cardiomyocytes. These findings represent a novel avenue to develop nanotechnology-based therapeutics and diagnostics in heart failure.
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, 6670 Bertner Street, MS R7-360.5, Houston, TX 77030, USA.|Escuela de Ingeniería y Ciencias, Tecnológico de Monterrey, Monterrey N.L., México 64849.|Catedra de Cardiología y Medicina Vascular, Escuela Nacional de Medicina, Tecnológico de Monterrey, Monterrey N.L., México 64710.
authors.forename: Guillermo U
authors.initials: GU
authors.lastname: Ruiz-Esparza
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, 6670 Bertner Street, MS R7-360.5, Houston, TX 77030, USA.|Escuela de Ingeniería y Ciencias, Tecnológico de Monterrey, Monterrey N.L., México 64849.
authors.forename: Victor
authors.initials: V
authors.lastname: Segura-Ibarra
authors.affiliation: DeBakey Heart and Vascular Center, Houston Methodist Hospital, 6565 Fannin Street, Suite 1901, Houston, TX 77030, USA.
authors.forename: Andrea M
authors.initials: AM
authors.lastname: Cordero-Reyes
authors.affiliation: DeBakey Heart and Vascular Center, Houston Methodist Hospital, 6565 Fannin Street, Suite 1901, Houston, TX 77030, USA.
authors.forename: Keith A
authors.initials: KA
authors.lastname: Youker
authors.affiliation: Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Rita E
authors.initials: RE
authors.lastname: Serda
authors.affiliation: DeBakey Heart and Vascular Center, Houston Methodist Hospital, 6565 Fannin Street, Suite 1901, Houston, TX 77030, USA.
authors.forename: Ana S
authors.initials: AS
authors.lastname: Cruz-Solbes
authors.affiliation: DeBakey Heart and Vascular Center, Houston Methodist Hospital, 6565 Fannin Street, Suite 1901, Houston, TX 77030, USA.
authors.forename: Javier
authors.initials: J
authors.lastname: Amione-Guerra
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, 6670 Bertner Street, MS R7-360.5, Houston, TX 77030, USA.
authors.forename: Kenji
authors.initials: K
authors.lastname: Yokoi
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, 6670 Bertner Street, MS R7-360.5, Houston, TX 77030, USA.
authors.forename: Dickson K
authors.initials: DK
authors.lastname: Kirui
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, 6670 Bertner Street, MS R7-360.5, Houston, TX 77030, USA.
authors.forename: Francisca E
authors.initials: FE
authors.lastname: Cara
authors.affiliation: Catedra de Cardiología y Medicina Vascular, Escuela Nacional de Medicina, Tecnológico de Monterrey, Monterrey N.L., México 64710.
authors.forename: Jesus
authors.initials: J
authors.lastname: Paez-Mayorga
authors.affiliation: Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Jose H
authors.initials: JH
authors.lastname: Flores-Arredondo
authors.affiliation: Catedra de Cardiología y Medicina Vascular, Escuela Nacional de Medicina, Tecnológico de Monterrey, Monterrey N.L., México 64710.
authors.forename: Carlos E
authors.initials: CE
authors.lastname: Guerrero-Beltrán
authors.affiliation: Catedra de Cardiología y Medicina Vascular, Escuela Nacional de Medicina, Tecnológico de Monterrey, Monterrey N.L., México 64710.
authors.forename: Gerardo
authors.initials: G
authors.lastname: Garcia-Rivas
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, 6670 Bertner Street, MS R7-360.5, Houston, TX 77030, USA.|Department of Medicine, Weill Cornell Medical College New York, NY, 10021, USA.
authors.forename: Mauro
authors.initials: M
authors.lastname: Ferrari
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, 6670 Bertner Street, MS R7-360.5, Houston, TX 77030, USA.
authors.forename: Elvin
authors.initials: E
authors.lastname: Blanco
authors.affiliation: Catedra de Cardiología y Medicina Vascular, Escuela Nacional de Medicina, Tecnológico de Monterrey, Monterrey N.L., México 64710.|DeBakey Heart and Vascular Center, Houston Methodist Hospital, 6565 Fannin Street, Suite 1901, Houston, TX 77030, USA.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Torre-Amione
mesh_terms: D000818:Animals; D001672:Biocompatible Materials; D004195:Disease Models, Animal; D006321:Heart / Q000502:physiology* / Q000503:physiopathology*; D006333:Heart Failure / Q000175:diagnosis* / Q000503:physiopathology / Q000628:therapy*; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009206:Myocardium; D032383:Myocytes, Cardiac / Q000502:physiology*; D049329:Nanostructures / Q000627:therapeutic use*; D011108:Polymers; D012825:Silicon
chemical_list: D001672:Biocompatible Materials; D011108:Polymers; D012825:Silicon
keywords: Cardiomyopathy; Heart failure; Nanoconstructs; Nanomedicine; Nanoparticles; Nanotechnology