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

Drug delivery advances\nrely on using nano- and microsized carriers\nto transfer therapeutic molecules, although challenges persist in\nincreasing the availability of new and even approved pharmaceutical\nproducts. Particle shape, a critical determinant in how these carriers\ndistribute within the body after administration, raises opportunities\nof using, for instance, micrometer-sized nonspherical particles for\nvascular targeting and thereby creating new prospects for precise\ndrug delivery to specific targeted areas. The versatility of polycrystalline\nsilicon microfabrication allows for significant variation in the size\nand shape of microchips, and so, in the current work, photolithography\nwas employed to create differently shaped polysilicon microchips,\nincluding cuboids, cubes, bars, and cylinders, to explore the influence\nof particle shape on cellular interactions. These microchips with\ndifferent shapes and lateral dimensions, accounting for surface areas\nin the range of ca. 15 to 120 μm<sup>2</sup> and corresponding\ntotal volumes of 0.4 to 27 μm<sup>3</sup>, serve as ideal models\nfor investigating their interactions with macrophages with diameters\nof ca. 20 μm. Side-scattering imaging flow cytometry was employed\nfor studying the interaction of label-free prepared microchips with\nRAW 264.7 macrophages. Using a dose of 3 microchips per cell, results\nshow that cuboids exhibit the highest cellular association (ca. 25%)\nand uptake (ca. 20%), suggesting their potential as efficient carriers\nfor targeted drug delivery to macrophages. Conversely, similarly sized\ncylinders and bar-shaped microchips exhibit lower uptakes of about\n8% and about 6%, respectively, indicating potential benefits in evading\nmacrophage recognition. On average, 1–1.5 microchips were internalized,\nand ca. 1 microchip was surface-bound per cell, with cuboids showing\nthe higher values overall. Macrophages respond to microchips by increasing\ntheir metabolic activity and releasing low levels of intracellular\nenzymes, indicating reduced toxicity. Interestingly, increasing the\nparticle dose enhances macrophage metabolic activity without significantly\naffecting enzyme release.