title: Enhanced gene delivery in porcine vasculature tissue following incorporation of adeno-associated virus nanoparticles into porous silicon microparticles.
abstract: There is an unmet clinical need to increase lung transplant successes, patient satisfaction and to improve mortality rates. We offer the development of a nanovector-based solution that will reduce the incidence of lung ischemic reperfusion injury (IRI) leading to graft organ failure through the successful ex vivo treatment of the lung prior to transplantation. The innovation is in the integrated application of our novel porous silicon (pSi) microparticles carrying adeno-associated virus (AAV) nanoparticles, and the use of our ex vivo lung perfusion/ventilation system for the modulation of pro-inflammatory cytokines initiated by ischemic pulmonary conditions prior to organ transplant that often lead to complications. Gene delivery of anti-inflammatory agents to combat the inflammatory cascade may be a promising approach to prevent IRI following lung transplantation. The rationale for the device is that the microparticle will deliver a large payload of virus to cells and serve to protect the AAV from immune recognition. The microparticle-nanoparticle hybrid device was tested both in vitro on cell monolayers and ex vivo using either porcine venous tissue or a pig lung transplantation model, which recapitulates pulmonary IRI that occurs clinically post-transplantation. Remarkably, loading AAV vectors into pSi microparticles increases gene delivery to otherwise non-permissive endothelial cells.
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX, USA.
authors.forename: Kellie I
authors.initials: KI
authors.lastname: McConnell
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Rhudy
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX, USA.
authors.forename: Kenji
authors.initials: K
authors.lastname: Yokoi
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX, USA.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Gu
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX, USA.
authors.forename: Aaron
authors.initials: A
authors.lastname: Mack
authors.affiliation: Department of Bioengineering, Rice University, Houston, TX, USA.
authors.forename: Junghae
authors.initials: J
authors.lastname: Suh
authors.affiliation: Methodist DeBakey Heart and Vascular Center Methodist Hospital, Houston, TX, USA.
authors.forename: Saverio
authors.initials: S
authors.lastname: La Francesca
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Sakamoto
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX, USA; Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX, USA. Electronic address: ritaserda@gmail.com.
authors.forename: Rita E
authors.initials: RE
authors.lastname: Serda
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000166:cytology / Q000378:metabolism*; D000229:Dependovirus / Q000276:immunology*; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression; D018014:Gene Transfer Techniques; D006801:Humans; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000821:virology; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D012825:Silicon / Q000737:chemistry*; D013552:Swine; D014680:Veins / Q000276:immunology / Q000821:virology
chemical_list: D012825:Silicon
keywords: Adeno-associated virus; Endothelium; Ex vivo perfusion; Inflammation; Lung; Mesoporous silicon