Tethered PEG Crowdedness Determining Shape and Blood Circulation Profile of Polyplex Micelle Gene Carriers

Abstract

Surface modification by poly(ethylene glycol) (PEG) onto gene carrier prepared through the electrostatic assembly of pDNA and polycation (polyplex) is a widely acknowledged strategy to advance their systemic application. In this regard, PEG crowdedness on the polyplex surface should give important contribution in determining blood circulation property; however its accurate quantification has never been demonstrated. We report here the first successful determination of PEG crowdedness for PEGylated polyplexes (polyplex micelle) formed from PEG–poly(l-lysine) block copolymers (PEG–PLys) and plasmid DNA (pDNA). Tethered PEG chains were found to adopt mushroom and even squeezed conformation by modulating PEG crowdedness through PLys segment length. Energetic analysis was conducted on the polyplex micelle to elucidate effect of PEG crowdedness on shape and clarify its essential role in regulating packaging structure of pDNA within the polyplex micelle. Furthermore, the PEG crowdedness significantly correlated to blood retention profile, approving its critical role on both shape and systemic circulation property.

Toroidal Packaging of pDNA into Block Ionomer Micelles Exerting Promoted in Vivo Gene Expression

“…We previously reported the significant anti-tumor effect 25 by this administration method to the subcutaneous xenograft of an intractable pancreatic tumor using our intensively studied rod-structured PMs. 18,23,[26][27][28][29][30] Therefore, the attained further increased efficacy of transgene expression using toroidal structures compared to rod-like structures would address the appreciable potential of this toroid structure and thus it should be explored in future studies as a distinct toroid-structured gene delivery system.…”

Shape control in engineering of polymeric nanoparticles for therapeutic delivery

“…Further tuning of the length of the PLL segment could be used to control the length of the rod-like shapes, with short PLL segments (degree of polymerization of 19) forming rod lengths greater than 200 nm, and longer PLL segments (degree of polymerization of 70) generating rods with lengths of 50–100 nm. 121, 122 It appears that the PEG chain crowdedness ( i.e. PEG chain density on micelle core surface) as a key factor in controlling micelle rod length.…”

In situ-preparation and characterization of silver-HEMA/PEGDA hydrogel matrix nanocomposites: Silver inclusion studies into hydrogel matrix

“…Neutral synthetic polymers can be generated from derivatives of poly(hydroxyethyl methacrylate) (PHEMA), poly(ethylene glycol) (PEG) and poly(vinyl alcohol) (PVA) (Ren et al, 2013;Tockary et al, 2013). Hydrogels based on PHEMA and PEG are the most widely studied materials and, also, the most used for biomedical applications due to their non-toxicity and non-immunogenic properties, making these types of hydrogels approved by the US Food and Drug Administration for a wide variety of medical uses such as human intravenous injection and oral and dermal applications .…”