Yake Allison M, Zahr Alisar S, Jerri Huda A, Pishko Michael V, Velegol Darrell
Department of Chemical Engineering, The Pennsylvania State University, University Park, Pennsylvania 16802, USA.
Biomacromolecules. 2007 Jun;8(6):1958-65. doi: 10.1021/bm070071r. Epub 2007 May 4.
Fabricating drug particles for therapeutic delivery and imaging presents important challenges in the design of the particle surfaces. Drug nanoparticle surfaces are currently functionalized with site-specific targeting ligands, biocompatible polymers, or fluorophore-polymer conjugates for specific imaging. However, if these functionalizations were to be synthesized on the drug carrier in localized, nanoscale regions on the particle surface, new schemes of drug delivery could be realized. Here we describe the use of our particle lithography technique that enables the synthesis of individual colloidal carrier assemblies that can be imaged and targeted to integrin-expressing cells. We show localized adhesion specificity for cells expressing the target integrin followed by receptor-mediated endocytosis. With the addition of localized delivery by adding drug nanoparticles to a specific region on the particle surface, our colloidal carrier assemblies have the potential to target, deliver therapeutic agents to, sense, and image diseased endothelium.
制造用于治疗递送和成像的药物颗粒在颗粒表面设计方面面临重大挑战。目前,药物纳米颗粒表面通过位点特异性靶向配体、生物相容性聚合物或荧光团 - 聚合物共轭物进行功能化,以实现特定成像。然而,如果这些功能化能够在颗粒表面的局部纳米级区域在药物载体上合成,那么就可以实现新的药物递送方案。在此,我们描述了使用我们的颗粒光刻技术,该技术能够合成可成像并靶向表达整合素的细胞的单个胶体载体组件。我们展示了对表达目标整合素的细胞的局部粘附特异性,随后是受体介导的内吞作用。通过在颗粒表面的特定区域添加药物纳米颗粒来实现局部递送,我们的胶体载体组件有潜力靶向、向患病内皮细胞递送治疗剂、进行传感和成像。