Cellular association and assembly of a multistage delivery system

Rita E. Serda, Aaron MacK, Merlyn Pulikkathara, Ana Maria Zaske, Ciro Chiappini, Jean R. Fakhoury, Douglas Webb, Biana Godin, Jodie L. Conyers, Xue W. Liu, James A. Bankson, Mauro Ferrari

Research output: Contribution to journalArticle

63 Scopus citations

Abstract

The realization that blood-borne delivery systems must overcome a multiplicity of biological barriers has led to the fabrication of a multistage delivery system (MDS) designed to temporally release successive stages of particles or agents to conquer sequential barriers, with the goal of enhancing delivery of therapeutic and diagnostic agents to the target site. In its simplest form, the MDS comprises stage-one porous silicon microparticles that function as carriers of second-stage nanoparticles. Cellular uptake of nontargeted discoidal silicon microparticles by macrophages is confirmed by electron and atomic force microscopy (AFM). Using superparamagnetic iron oxide nanoparticles (SPIONs) as a model of secondary nanoparticles, successful loading of the porous matrix of silicon microparticles is achieved, and retention of the nanoparticles is enhanced by aminosilylation of the loaded microparticles with 3-aminopropyltriethoxysilane. The impact of silane concentration and reaction time on the nature of the silane polymer on porous silicon is investigated by AFM and X-ray photoelectron microscopy. Tissue samples from mice intravenously administered the MDS support co-localization of silicon microparticles and SPIONs across various tissues with enhanced SPION release in spleen, compared to liver and lungs, and enhanced retention of SPIONs following silane capping of the MDS. Phantom models of the SPION-loaded MDS display negative contrast in magnetic resonance images. In addition to forming a cap over the silicon pores, the silane polymer provides free amines for antibody conjugation to the microparticles, with both VEGFR-2- and PECAM-specific antibodies leading to enhanced endothelial association. This study demonstrates the assembly and cellular association of a multiparticle delivery system that is biomolecularly targeted and has potential for applications in biological imaging.

Original languageEnglish (US)
Pages (from-to)1329-1340
Number of pages12
JournalSmall
Volume6
Issue number12
DOIs
StatePublished - Jun 21 2010

Keywords

  • Drug delivery
  • Imaging
  • Microparticles
  • Nanoparticles
  • Porous materials

ASJC Scopus subject areas

  • Biomaterials
  • Engineering (miscellaneous)
  • Biotechnology
  • Medicine(all)

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