Probing the Role of Charged Functional Groups on Nanoparticles Grafted with Polyglycerol in Protein Adsorption and Cellular Uptake

Abstract

In biofluids, charged functional groups on the surface of nanoparticles (NPs) interact with cells through the protein corona. However, the cascade effects of charged groups on corona formation and cellular uptake remain unclear. Herein, carboxy, sulfate, and amino groups are quantitatively introduced at the periphery of polyglycerol (PG)‐grafted nanodiamond and superparamagnetic iron oxide NP to probe their roles in corona formation and cellular uptake. The uptake efficiency and intracellular aggregation state of NPs are revealed to correlate with protein affinity of the charged groups; sulfate at lower density and carboxylate exhibit no affinity to proteins, inducing negligible or no cellular uptake. In contrast, sulfate at higher density and ammonium associate with fetal bovine serum proteins to alter the aggregation state of the internalized NPs. It is further demonstrated that the distinct protein corona profiles on NP‐PG‐OSO3− and NP‐PG‐NH3+ surfaces dictate their uptake mechanism. The protein corona of NP‐PG‐OSO3− suppresses cellular uptake via downregulation of macropinocytosis and clathrin‐mediated endocytosis, whereas that of NP‐PG‐NH3+ enhances uptake through upregulation of macropinocytosis and caveolae‐mediated endocytosis. This study clarifies the elusive role of the charged groups in protein adsorption and cellular uptake, which sheds light on NP design for controlled cellular uptake and theranostics in nanomedicine.

Artificial engineering of the protein corona at bio-nano interfaces for improved cancer-targeted nanotherapy

“…One probable reason for different interactions of NPs in the biological systems with multiple cell types is referred to the distinct variation in zeta potential of NPs upon exposure to cell paracrine factors. NPs with low zeta potential do not potentially interact with the cells and show a lower success of cell uptake [54,156].…”

“…Also, the latter can be divided into four routes: clathrin-and caveolae-mediated endocytosis, clathrin-and caveolae-independent endocytosis, and macropinocytosis [158]. However, the presence of the PC can vary the capability of NPs to interact with cells and the corresponding cell uptake [156]. Also, it has been shown that the size, shape, and PC can change the endocytosis pathways; however they do not alter the exocytosis mechanism [159].…”

Development of a Lysine-Based Poly(ester amide) Library with High Biosafety and a Finely Tunable Structure for Spatiotemporal-Controlled Protein Delivery

“…When x became 8, the number of carbon atoms in the main chain of Lys-aaPEA and the size of Lys-aaPEA@INS decreased with increasing y . The main cause of this phenomenon could be the stronger hydrophobic interaction; longer carbon chains improved the hydrophobicity of total Lys-aaPEA, leading to tighter structures with smaller sizes of nanocomposites. , Moreover, it was remarkable that Lys-aaPEA@INS with smaller sizes usually exhibited a higher ζ potential. In phosphate-buffered saline at pH 7.4 (PBS, pH 7.4), the polymers could form a stable nanosized suspension.…”

Polyglycerol Functionalized 10B Enriched Boron Carbide Nanoparticle as an Effective Bimodal Anticancer Nanosensitizer for Boron Neutron Capture and Photothermal Therapies

“…[44] Since the proteins adsorbed on the surface of NPs are well known to facilitate its recognition by mononuclear phagocyte system (MPS), the 10 B 4 C-PG in this study is supposed to be opsonized through protein adsorption. Although we reported that PG coating for NPs (NP = ND and SPION) avoids protein corona formation, [45] a much more negative zeta potential of 10 B 4 C-PG (−52 mV) than the ND-PG (around −5 mV) as shown in Figure S8, Supporting Information, is considered to induce protein attraction through electrostatic interaction, which is reported to be one of the primary forces between proteins and the NP surfaces. [44] The resulting opsonized 10 B 4 C-PG is considered to be recognized and trapped in liver and spleen.…”