Physicochemical and Surface Properties of Nanoparticles: Effects on Cellular Pathway and Uptake

Nanoparticles (NPs) are promising tools in biomedical applications. Their unique physicochemical properties, such as controllable size, tunable shape, and versatile surface functionality, provide significant advantages in targeted delivery and controlled release. Despite the large progress, NP-based drug delivery systems still face a major challenge, i.e., NPs often demonstrate less therapeutic improvements than expected. The disparity mainly arises from the incomplete understanding of NP behaviors in the complex biological environments, especially their cellular uptake mechanisms, and thus, the performances of NPs are generally not optimized. A comprehensive understanding of how NP properties influence cellular uptake is essential for the design of high-performance delivery systems. This review summarizes recent advancements in the investigation of NP cellular uptake pathways and factors, such as NP size, shape, and surface functionality, which affect the cellular uptake processes. The physical and chemical properties of NPs can be modulated to control the cellular uptake pathway and enhance the cellular uptake efficiency, thus ultimately improving the bioavailability, efficacy, and safety. It aims to provide new insights for the design of NPs, ultimately advancing their applications in biomedical therapy.