PEGylated polyplex micelles from triblock catiomers with spatially ordered layering of condensed pDNA and buffering units for enhanced intracellular gene delivery.
An A-B-C type triblock copolymer, tandemly aligning two types of polycations with different pKa values in a single polymer strand, was developed for the construction of novel polyplex micelles, satisfying a high DNA condensing ability as well as a proton buffering activity directed to elevating gene transfection. The micelle might feature the distinctive three-layered structure, where an inner polyplex layer of condensed pDNA with poly(l-lysine) (pKa approximately 9.4) as the C segment is successively wrapped with an intermediate layer of poly[(3-morpholinopropyl)aspartamide] (B segment) with a comparatively low pKa of approximately 6.2, to provide a buffering effect, and an outer PEG layer (A segment) as a biocompatible palisade.
Fukushima
Shigeto
S
Department of Materials Science and Engineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
Miyata
Kanjiro
K
Nishiyama
Nobuhiro
N
Kanayama
Naoki
N
Yamasaki
Yuichi
Y
Kataoka
Kazunori
K
D001224:Aspartic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry*; D002021:Buffers; D002412:Cations; D002460:Cell Line; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000138:chemical synthesis / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D008823:Micelles; D009025:Morpholines / Q000008:administration & dosage / Q000737:chemistry*; D010957:Plasmids / Q000008:administration & dosage / Q000737:chemistry* / Q000235:genetics; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry*; D011107:Polylysine / Q000008:administration & dosage / Q000737:chemistry*; D014162:Transfection
D002021:Buffers; D002412:Cations; D008823:Micelles; D009025:Morpholines; C499728:poly (3-morpholinopropyl) aspartamide; D011107:Polylysine; D001224:Aspartic Acid; D011092:Polyethylene Glycols