Enhanced gene delivery in porcine vasculature tissue following incorporation of adeno-associated virus nanoparticles into porous silicon microparticles

Kellie I. McConnell, Jessica Rhudy, Kenji Yokoi, Jianhua Gu, Aaron Mack, Junghae Suh, Saverio La Francesca, Jason Sakamoto, Rita E. Serda

Research output: Contribution to journalArticle

10 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)113-121
Number of pages9
JournalJournal of Controlled Release
Volume194
DOIs
StatePublished - Nov 28 2014

Keywords

  • Adeno-associated virus
  • Endothelium
  • Ex vivo perfusion
  • Inflammation
  • Lung
  • Mesoporous silicon

ASJC Scopus subject areas

  • Pharmaceutical Science

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