Rod-to-Globule Transition of pDNA/PEG-Poly(l-Lysine) Polyplex Micelles Induced by a Collapsed Balance Between DNA Rigidity and PEG Crowdedness

• Published in: Small (Weinheim an der Bergstrasse, Germany) Germany), 2016-03, Vol.12 (9), p.1193-1200
• Main Authors: Tockary, Theofilus A., Osada, Kensuke, Motoda, Yusuke, Hiki, Shigehiro, Chen, Qixian, Takeda, Kaori M., Dirisala, Anjaneyulu, Osawa, Shigehito, Kataoka, Kazunori
• Format: Article
• Language: English
• Subjects: Block copolymers; Deoxyribonucleic acid; DNA; DNA - chemistry; DNA packaging; gene delivery; Hydrogen-Ion Concentration; Lysine; Micelles; nanorods; Nanotechnology; Plasmids; Plasmids - chemistry; Polyethylene glycol; Polyethylene Glycols - chemical synthesis; Polyethylene Glycols - chemistry; Polylysine - chemistry; polymers; polyplex micelles; polyplex micelles, micelles; Rigidity; Supports
• ISSN: 1613-6810; 1613-6829
• DOI: 10.1002/smll.201501815

The role of poly(ethylene‐glycol) (PEG) in rod‐shaped polyplex micelle structures, having a characteristic core of folded plasmid DNA (pDNA) and a shell of tethered PEG chains, is investigated using PEG‐detachable polyplex micelles. Rod shapes undergo change to compacted globule shapes by removal of PEG from polyplex micelles prepared from block copolymer with acid‐labile linkage between PEG and poly(l‐lysine) (PLys) through exposure to acidic milieu. This structural change supports the previous investigation on the rod shapes that PEG shell prevents the DNA structure from being globule shaped as the most favored structure in minimizing surface area. Noteworthy, despite the PEG is continuously depleted, the structural change does not occur in gradual shortening manner but the rod shapes keep their length unchanged and abruptly transform into globule shapes. Analysis of PEG density reveals the transition occurred when tethered PEG of rod shapes has decreased to a critical crowdedness, i.e., discontacted with neighboring PEG, which eventually illuminates another contribution, rigidity of DNA packaged as bundle in the rod shapes, in addition to the steric repulsion of PEG, in sustaining rod shapes. This investigation affirms significant role of PEG and also DNA rigidity as bundle in the formation of rod‐shaped structures enduring the quest of compaction of charge‐neutralized DNA in the polyplex micelles. Shape‐regulating contributors in rod‐shaped polyplex micelle gene carriers are investigated through poly(ethylene‐glycol) (PEG)‐detachable polyplex micelles prepared from plasmid DNA and PEG–poly(l‐lysine) block copolymer with an acid‐cleavable linker. This study affirms the significant contribution of PEG and rigidity of packaged DNA as a bundle to sustain polyplex micelles in rod shape.