Bowl-Shaped Mesoporous Polydopamine Nanoparticles for Size-Dependent Endocytosis into HeLa Cells

A comprehensive study of cellular internalization mechanisms of nanoparticles is crucial to optimize their drug delivery efficacy, as endocytosis pathways will likely determine their biological fate. Particularly for polydopamine bowl-shaped mesoporous nanoparticles (PDA bowls), their anisotropic morphology provides enhanced cellular internalization efficiency with respect to their spherical counterparts, though the mechanism of this is not yet fully understood. Herein, we report a size-controlled synthesis of PDA bowls by changing different reaction parameters and investigated their size-dependent endocytosis pathways in the HeLa cell line. The cellular internalization behavior of PDA bowls was investigated by using a suite of characterization techniques including flow cytometry, confocal microscopy, and transmission electron microscopy. Obtained results demonstrated that the uptake efficiency of PDA bowls is significantly dependent on their size. Moreover, the size of bowls also plays an important role in the endocytosis pathways followed to internalize them into cells, which was investigated by blocking certain endocytosis pathways with biological inhibitors. Taken together, this work provides fundamental understanding of the impact of reaction parameters on size-controlled synthesis of PDA bowls and reveals the role of their size in regulating the cellular internalization pathways, providing key structure–function information for these unique particles, which pave the way to the optimization of engineering drug nanocarriers in cancer treatment with higher efficacy.