Protein Corona Formation on Colloidal Polymeric Nanoparticles and Polymeric Nanogels: Impact on Cellular Uptake, Toxicity, Immunogenicity, and Drug Release Properties

Abstract

The adsorption of biomolecules to the surface of nanoparticles (NPs) following administration into biological environments is widely recognized. In particular, the "protein corona" is well understood in terms of formation kinetics and impact upon the biological interactions of NPs. Its presence is an essential consideration in the design of therapeutic NPs. In the present study, the protein coronas of six polymeric nanoparticles of prospective therapeutic use were investigated. These included three colloidal NPs-soft core-multishell (CMS) NPs, plus solid cationic Eudragit RS (EGRS), and anionic ethyl cellulose (EC) nanoparticles-and three nanogels (NGs)-thermoresponsive dendritic-polyglycerol (dPG) nanogels (NGs) and two amino-functionalized dPG-NGs. Following incubation with human plasma, protein coronas were characterized and their biological interactions compared with pristine NPs. All NPs demonstrated protein adsorption and increased hydrodynamic diameters, although the solid EGRS and EC NPs bound notably more protein than the other tested particles. Shifts toward moderately negative surface charges were also observed for all corona bearing NPs, despite varied zeta potentials in their pristine states. While the uptake and cellular adhesion of the colloidal NPs in primary human keratinocytes and human umbilical vein endothelial cells were significantly decreased when bearing the protein corona, no obvious impact was seen in the NGs. By contrast, corona bearing NGs induced marked increases in cytokine release from primary human macrophages not seen with corona bearing colloidal NPs. Despite this, no apparent enhancement to in vitro toxicity was noted. Finally, drug release from EGRS and EC NPs was assessed, where a decrease was seen in the EGRS NPs alone. Together these results provide a direct comparison of the physical and biological impact the protein corona has on NPs of widely varied character and in particular highlights a distinction between the corona's effects on NGs and colloidal NPs.

Gadolinium Oxide Nanoparticles Induce Toxicity in Human Endothelial HUVECs via Lipid Peroxidation, Mitochondrial Dysfunction and Autophagy Modulation

“…The hydrodynamic size of GO NPs were found to occur almost 4-times bigger in complete culture media (DMEM + 10% FBS) than were in TEM measurement suggesting significant agglomeration tendency. Particle agglomeration was significantly low in media than in water which is the indicative of media ingredients modifying NPs surfaces and colonization [ 48 , 49 , 50 ]. A variety of potentially interacting components in relevant aqueous fluids like culture media may influence the NPs native property.…”

Branched and Dendritic Polymer Architectures: Functional Nanomaterials for Therapeutic Delivery

“…The formation of this protein corona is dependent on nanoparticle size, surface charge, and exterior chemical composition. 54,55 A common strategy is to functionalise the nanocarrier exterior with a stealth non-fouling polymer such as poly(ethylene glycol) (PEG), poly(poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC), poly(2-oxazoline) (Pox), or poly(poly(ethyl ethylene phosphate) (PEEP). 56,57 These hydrophilic polymers form a hydration layer which can hinder protein absorption and thus reduce MPS clearance.…”

High Surface Reactivity and Biocompatibility of Y2O3 NPs in Human MCF-7 Epithelial and HT-1080 Fibro-Blast Cells

“…A variety of potential interacting component in relevant aqueous fluids may affect NPs native property prior to biological interaction [25,26]. Zeta potential and hydrodynamic sizes of NPs play crucial role in their secondary surface formation or coronization [27,28]. In this study, as determined by DLS, zeta potential of Y 2 O 3 NPs suspension in complete culture media (−27.0 ± 1.2 mV) was much better than that in water (−16.0 ± 4.2 mV), PBS (−6.0 ± 2.4mV) and serum free culture media (−10.0 ± 4.0 mV).…”

“…Protein adsorption to NPs is a dynamic process in fluids be it culture media, blood or other bio fluids independent of nature of the NPs either polymeric [28] or metallic [30]. One of the most notable alterations when NP is under biological fluids is the formation of NP-protein corona [28]. In addition to protein coating, there are reports about non-protein coating on Y 2 O 3 NPs to achieve desirable outcome.…”