Limited Impact of the Protein Corona on the Cellular Uptake of PEGylated Zein Micelles by Melanoma Cancer Cells.

Jitkasem Meewan,Abdullah R Alzahrani,Sukrut Somani,Richard Burchmore,Craig Irving,Suzanne Mcgill,Craig W Roberts,Christine Dufès,Valerie A Ferro,Margaret Mullin,Partha Laskar,Stefan Weidt,Stuart Woods

doi:10.3390/pharmaceutics14020439

Abstract

The formation of a protein layer “corona” on the nanoparticle surface upon entry into a biological environment was shown to strongly influence the interactions with cells, especially affecting the uptake of nanomedicines. In this work, we present the impact of the protein corona on the uptake of PEGylated zein micelles by cancer cells, macrophages, and dendritic cells. Zein was successfully conjugated with poly(ethylene glycol) (PEG) of varying chain lengths (5K and 10K) and assembled into micelles. Our results demonstrate that PEGylation conferred stealth effects to the zein micelles. The presence of human plasma did not impact the uptake levels of the micelles by melanoma cancer cells, regardless of the PEG chain length used. In contrast, it decreased the uptake by macrophages and dendritic cells. These results therefore make PEGylated zein micelles promising as potential drug delivery systems for cancer therapy.

Highlights

Zein, a prolamin protein extracted from corn, has been widely used in food, pharmaceutical, and biomedical applications because of its generally regarded as safe (GRAS)status [1,2,3]
Gref et al revealed that the with poly(ethylene glycol) (PEG) and was able to assemble into micelles, entrapping a model hydrophobic type and amount of the corona proteins were determined by the PEG chain length and substance, Nile red. methoxy PEG (mPEG)‐zein micelles could deliver Nile red into the B16‐F10‐luc‐G5 density at the particle surface as well as the nature of the core material [25]
Regardless of the PEG chain length, thereby minimizing the adsorption of proteins on the micelles. It was shown for the first time that the presence of Human Plasma (HP) did not have any impact on the uptake of mPEG‐zein micelles by the melanoma cancer cells, independent of the molecular weight (MW) PEG used in the formulations

Summary

Introduction

Status [1,2,3]. It is classified into four main types, depending on their molecular weight (MW), charge, and solubility [4]. Α-zein, consists of 75–80% of the total zein with a MW of 19–24 kDa, while β-zein is a polymer of 17–18 kDa. γ-zein contains two parts of 27 kDa and 18 kDa, and δ-zein is a minor fraction of 10 kDa [5,6,7,8]. It contains more than 50% lipophilic amino acids, leading to insolubility in water. Its high glutamine content makes it insoluble in absolute alcohol [9], but facilitates conjugation with biomolecules via its N-terminal group

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