Cellular Association and Assembly of a Multistage Delivery System

Abstract

The realization that blood-borne delivery systems must overcome a multiplicity of biological barriers has led to the fabrication of a multi-stage delivery system (MDS) designed to temporally release successive stages of particles or agents to conquer sequential barriers with a goal of enhancing delivery of therapeutic and diagnostic agents to the target site. In its simplest appearance, the MDS is comprised of stage one porous silicon microparticles that function as carriers of second stage nanoparticles. In this study, cellular uptake of non-targeted discoidal silicon microparticles by macrophages was confirmed by electron and atomic force microscopy (AFM). Using SPIONs as a model of secondary nanoparticles, successful loading of the porous matrix of silicon microparticles was achieved and retention of the nanoparticles was enhanced by aminosilylation of the loaded microparticle with 3-aminopropyltriethoxysilane. The impact of silane concentration and reaction time on the nature of the silane polymer on porous silicon was investigated by AFM and X-ray photoelectron microscopy. Tissue samples from mice intravenously administered the MDS supported 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 displayed negative contrast in magnetic resonance images. In addition to forming a cap over the silicon pores, the silane polymer provided free amines for antibody conjugation to the microparticles, with both VEGFR-2 and PECAM specific antibodies leading to enhanced endothelial association. This study demonstrates assembly and cellular association of a multi-particle delivery system that is bio-molecularly targeted and has potential for applications in biological imaging.

Nanostructured porous silicon in preclinical imaging: Moving from bench to bedside

“…5). 74,75 Magnevist Ò (Bayer Schering Pharma, Berlin-Wedding, Germany), gadofullerenes, and gadonanotubes were loaded inside the pores of quasihemispherical and discoidal PSi particles, and the nanoconstructed combinations boosted the longitudinal proton relaxivity (r1) with: Magnevist Ò , r1 % 14 mM À1 s À1 /Gd 31 ion (;8.15 Â 10 17 mM À1 s À1 /construct); gadofullerenes, r1 % 200 mM À1 s À1 /Gd 31 ion (;73 Â 10 19 mM À1 s À1 / construct); gadonanotubes, r1 % 150 mM À1 s À1 /Gd 31 ion (;23 Â 10 19 mM À1 s À1 /construct). These relaxivity values were about 4-50 times larger than those of clinically available gadolinium-based agents (;4 mM À1 s À1 /Gd 31 ion).…”

Physicochemical Properties Affect the Synthesis, Controlled Delivery, Degradation and Pharmacokinetics of Inorganic Nanoporous Materials

“…These conjugations convert the unstable hydrophobic surface of pSi into a stable hydrophilic surface with a negative charge. In addition, these new surface modifications permit further functionalization enabling the introduction of carboxyl and amine groups [37], PEGylation [38], recognition molecules [39,40] porphyrins for photodynamic therapy [41], and fluorescent probes [42] allowing for the biodistribution assessment of pSi particles when the photoluminescence [35] is not possible.…”

Les nanoparticules de silice mésoporeuse pour combattre le cancer

“…Uniform loading of the S1MP nanoporous matrix with S2NPs has been shown with iron oxide nanoparticles [13]. Figure 3A shows a TEM image of two silicon microparticles after sectioning with a microtome.…”