Cuboids Prevail When Unraveling the Influence of Microchip Geometry on Macrophage Interactions and Metabolic Responses

Abstract

Drug delivery advances rely on using nano- and micro-sized carriers to transfer therapeutic molecules, although challenges persist in increasing the availability of new and even approved pharmaceutical products. Particle shape, a critical determinant in how these carriers distribute within the body after administration, raises opportunities of using, for instance, micron-sized non-spherical particles for vascular targeting, and thereby creating new prospects for precise drug delivery to specific targeted areas. The versatility of polycrystalline silicon microfabrication allows for significant variation in the size and shape of microchips and so, in the current work, photolithography was employed to create different shaped polysilicon microchips, including cuboids, cubes, bars, and cylinders, to explore the influence of particle shape on cellular interactions. These microchips with different shapes and lateral dimensions, accounting for surface areas in the range ca. 15 to 120 µm² and corresponding total volumes of 0.4 to 27 µm³, serve as ideal models for investigating their interactions with macrophages with diameters of ca. 20 µm. Side-scattering imaging flow cytometry was employed for studying the interaction of label-free prepared microchips with RAW 264.7 macrophages. Using a dose of 3 microchips per cell, results show that cuboids exhibit the highest cellular association (ca. 25 %) and uptake (ca. 20 %), suggesting their potential as efficient carriers for targeted drug delivery to macrophages. Conversely, similarly sized cylinders and bar-shaped microchips exhibit lower uptake of ca. 8 % and ca. 6 %, respectively, indicating potential benefits in evading macrophage recognition. On average, 1-1.5 microchips were internalized and ca. 1 microchip was surface-bound per cell, with cuboids showing the higher values overall. Macrophages respond to microchips by increasing their metabolic activity and releasing low levels of intracellular enzymes, indicating reduced toxicity. Interestingly, increasing the particle dose enhances macrophage metabolic activity, without significantly affecting enzyme release.