Department of Nanomedicine and Biomedical Engineering, University of Texas Health Science Center (UTHSC), Houston, TX 77030, USA.
Small. 2010 Jun 21;6(12):1329-40. doi: 10.1002/smll.201000126.
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.
认识到血液传递系统必须克服多种生物屏障，导致了多阶段传递系统（MDS）的制造，旨在按时间顺序释放连续阶段的颗粒或药物以克服连续的障碍，目的是增强治疗和诊断剂递送到靶部位。在其最简单的形式中，MDS 由第一阶段多孔硅微球组成，作为第二阶段纳米颗粒的载体。通过电子和原子力显微镜（AFM）证实了非靶向盘状硅微球被巨噬细胞摄取。使用超顺磁性氧化铁纳米颗粒（SPIONs）作为二次纳米颗粒的模型，成功地负载了硅微球的多孔基质，并通过用 3-氨基丙基三乙氧基硅烷对负载的微球进行氨硅烷化来增强纳米颗粒的保留。通过 AFM 和 X 射线光电子能谱研究了硅烷浓度和反应时间对多孔硅中硅烷聚合物性质的影响。用 MDS 静脉给药的小鼠组织样本支持硅微球和 SPION 在各种组织中的共定位，与肝脏和肺部相比，SPION 在脾脏中的释放增强，并且在 MDS 硅烷封端后 SPION 的保留增强。负载 SPION 的 MDS 的幻影模型在磁共振图像中显示出负对比。硅烷聚合物除了在硅孔上形成帽外，还提供游离的胺用于微球与抗体的缀合，VEGFR-2 和 PECAM 特异性抗体都导致内皮细胞的结合增强。本研究证明了多颗粒传递系统的组装和细胞关联，该系统具有生物分子靶向性，并且在生物成像应用中具有潜力。
