TY - JOUR
T1 - Enhanced gene delivery in porcine vasculature tissue following incorporation of adeno-associated virus nanoparticles into porous silicon microparticles
AU - McConnell, Kellie I.
AU - Rhudy, Jessica
AU - Yokoi, Kenji
AU - Gu, Jianhua
AU - Mack, Aaron
AU - Suh, Junghae
AU - La Francesca, Saverio
AU - Sakamoto, Jason
AU - Serda, Rita E.
PY - 2014/11/28
Y1 - 2014/11/28
N2 - 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.
AB - 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.
KW - Adeno-associated virus
KW - Endothelium
KW - Ex vivo perfusion
KW - Inflammation
KW - Lung
KW - Mesoporous silicon
UR - http://www.scopus.com/inward/record.url?scp=84907189306&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84907189306&partnerID=8YFLogxK
U2 - 10.1016/j.jconrel.2014.08.020
DO - 10.1016/j.jconrel.2014.08.020
M3 - Article
C2 - 25180449
AN - SCOPUS:84907189306
VL - 194
SP - 113
EP - 121
JO - Journal of Controlled Release
JF - Journal of Controlled Release
SN - 0168-3659
ER -