The Institute for Drug Research, the School of Pharmacy, the Faculty of Medicine, The Center for Nanoscience and Nanotechnology, The Hebrew University of Jerusalem, Jerusalem 9112192, Israel.
The Unit for Nanoscopic Characterization, The Center for Nanoscience and Nanotechnology, The Hebrew University of Jerusalem, Jerusalem 91904, Israel.
ACS Appl Mater Interfaces. 2024 Oct 30;16(43):58168-58179. doi: 10.1021/acsami.4c09565. Epub 2024 Aug 23.
Exploiting the chirality of nanometric structures to modulate biological systems is an emerging and compelling area of research. In this study, we reveal that chiral polyurea nanocapsules exhibit significant stereoselective interactions with albumins from various sources despite their nearly neutral surface potential. Moreover, these interactions can be modulated by altering the nanocapsule surface composition, offering new opportunities to impact their distribution and, if used as a drug delivery system, the pharmacokinetics of the drug. Notably, these interactions promote preferential cellular internalization of only one chiral configuration. We synthesized chiral polyurea nanocapsules with reproducible sizes via interfacial polymerization between toluene 2,4-diisocyanate and d- or l-lysine enantiomers on a volatile oil-in-water emulsion interface, followed by solvent evaporation. Further synthesis optimization reduced the capsule size to a range compatible with administration, and capsules with alternating chiral patterns were also produced. The stereoselective interactions with albumins were assessed through capsule size changes, fluorescence quenching, and surface charge measurements. Biocompatibility, stability, and cellular internalization were evaluated. Additionally, scanning transmission electron and atomic force microscopy were carried out to assess the capsule shape, surface composition, and morphology. We discovered that d-nanocapsules exhibited 2.1-2.6 times greater albumin adsorption compared with their l-counterparts. This difference is attributed to the distinct morphology of d-nanocapsules, characterized by a more concave shape, central depression, and rougher surface. The extent of adsorption could be finely tuned by adjusting the d- and l-lysine monomer ratios during synthesis. Both chiral configurations demonstrated biocompatibility and stability with d-nanocapsules showing a 2.5-fold increase in cellular internalization.
利用纳米结构的手性来调节生物系统是一个新兴且引人关注的研究领域。在这项研究中，我们揭示了尽管手性聚脲纳米胶囊的表面电势接近中性，但它们仍与来自不同来源的白蛋白表现出显著的立体选择性相互作用。此外，通过改变纳米胶囊表面组成可以调节这些相互作用，为影响其分布提供了新的机会，如果将其用作药物传递系统，则可以影响药物的药代动力学。值得注意的是，这些相互作用促进了仅一种手性构象的优先细胞内化。我们通过界面聚合法在挥发性油包水乳液界面上将甲苯 2,4-二异氰酸酯和 d-或 l-赖氨酸对映体之间进行界面聚合，从而合成了具有重现性尺寸的手性聚脲纳米胶囊，随后进行溶剂蒸发。进一步的合成优化将胶囊尺寸缩小到适合给药的范围，并产生了具有交替手性图案的胶囊。通过胶囊尺寸变化、荧光猝灭和表面电荷测量评估了与白蛋白的立体选择性相互作用。评估了生物相容性、稳定性和细胞内化。此外，还进行了扫描透射电子显微镜和原子力显微镜以评估胶囊形状、表面组成和形态。我们发现 d-纳米胶囊与 l-纳米胶囊相比，对白蛋白的吸附量增加了 2.1-2.6 倍。这种差异归因于 d-纳米胶囊的独特形态，其特征是更凹的形状、中央凹陷和更粗糙的表面。通过在合成过程中调整 d-和 l-赖氨酸单体的比例，可以精细地调节吸附量。两种手性构型都表现出生物相容性和稳定性，d-纳米胶囊的细胞内化增加了 2.5 倍。
