Effect of Molecular Architecture on Cell Interactions and Stealth Properties of PEG

Abstract

PEGylation, covalent attachment of PEG to therapeutic biomolecules, in which suboptimal pharmacokinetic profiles limiting their therapeutic utility are of concern, is a widely applied technology. However, this technology has been challenged by reduced bioactivity of biomolecules upon PEGylation and immunogenicity of PEG triggering immune response and abrogating clinical efficacy, which collectively necessitate development of stealth polymer alternatives. Here we demonstrate that comb-shape poly[oligo(ethylene glycol) methyl ether methacrylate] (POEGMA), a stealth polymer alternative, has a more compact structure than PEG and self-organize into nanoparticles in a molecular weight dependent manner. Most notably, we show that comb-shape POEGMA promotes significantly higher cellular uptake and exhibits less steric hindrance imposed on the conjugated biomolecule than PEG. Collectively, comb-shape POEGMA offers a versatile alternative to PEG for stealth polymer-biomolecule conjugation applications.

Tunable Degradation of Copolymers Prepared by Nitroxide-Mediated Radical Ring-Opening Polymerization and Point-by-Point Comparison with Traditional Polyesters

“…Although OEGMA-based materials are considered to be non-toxic and potentially stealth, 16,[48][49][50][51][52][53][54][55][56][57] inserting multiple MPDL units group could modify the toxicity of the resulting copolymers.…”

Antimicrobial and Anti‐Biofilm Activities of Surface Engineered Polycationic Albumin Nanoparticles with Reduced Hemolytic Activity

“…Nevertheless, we observed higher potency against P. aeruginosa where the MIC readings remained unchanged. This reported higher antimicrobial activity is beneficial and can be an inherent advantage over AMPs such as the magainin, a 22‐amino‐acid linear antimicrobial peptide currently undergoing clinical trials showing effective concentrations of 55.96 ± 2.84 µ m against P. aeruginosa . These results further demonstrate the utility of PEG density and molecular weight as strategies to achieve facile customization of apparent surface charge, tuning of antimicrobial potency and toxicity.…”

Anticancer drug delivery to cancer cells using alkyl amine-functionalized nanodiamond supraparticles

“…[21][22][23] Additionally, the lower drug efficacies of conventional nanocarriers are likely due to PEG moieties on their constructs that generally inhibit interactions with cells. 24,25 To clarify the effective transmembrane permeation properties of ND-SPs, uorescence live cell imaging was performed (Fig. 5).…”