Cellular association and assembly of a multistage delivery system.
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.
Department of Nanomedicine and Biomedical Engineering, University of Texas Health Science Center (UTHSC), Houston, TX 77030, USA. Rita.Serda@uth.tmc.edu
Rita E
RE
Serda
Aaron
A
Mack
Merlyn
M
Pulikkathara
Ana Maria
AM
Zaske
Ciro
C
Chiappini
Jean R
JR
Fakhoury
Douglas
D
Webb
Biana
B
Godin
Jodie L
JL
Conyers
Xue W
XW
Liu
James A
JA
Bankson
Mauro
M
Ferrari
D000818:Animals; D002460:Cell Line; D016503:Drug Delivery Systems; D051379:Mice; D018625:Microscopy, Atomic Force; D053758:Nanoparticles / Q000737:chemistry*; D036103:Nanotechnology; D056951:Photoelectron Spectroscopy; D016062:Porosity