Aqueous solution behaviour and membrane disruptive activity of pH-responsive PEGylated pseudo-peptides and their intracellular distribution

Biomaterials
Rongjun ChenNigel K H Slater

Abstract

The effect of PEGylation on the aqueous solution properties and cell membrane disruptive activity of a pH-responsive pseudo-peptide, poly(l-lysine iso-phthalamide), has been investigated by dynamic light scattering, haemolysis and lactate dehydrogenase (LDH) assays. Intracellular trafficking of the polymers has been examined using confocal and fluorescence microscopy. With increasing degree of PEGylation, the modified polymers can form stabilised compact structures with reduced mean hydrodynamic diameters. Poly(l-lysine iso-phthalamide) with a low degree of PEGylation (17.4 wt%) retained pH-dependent solution behaviour and showed enhanced kinetic membrane disruptive activity compared to the parent polymer. It facilitated trafficking of endocytosed materials into the cytoplasm of HeLa cells. At levels of PEGylation in excess of 25.6 wt%, the modified polymers displayed a single particle size distribution unresponsive to pH, as well as a decrease in cell membrane lytic ability. The mechanism involved in membrane destabilisation was also investigated, and the potential applications of these modified polymers in drug delivery were discussed.

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Citations

Jun 11, 2011·Langmuir : the ACS Journal of Surfaces and Colloids·Shengwen ZhangRongjun Chen
Jan 1, 2010·Annual Review of Chemical and Biomolecular Engineering·William B LiechtyNicholas A Peppas
Jun 12, 2010·Journal of Biomaterials Science. Polymer Edition·Sariah KhormaeeNigel K H Slater
May 18, 2010·Biomaterials·Andrew L LynchNigel K H Slater
Oct 19, 2009·Advanced Materials·William B LiechtyNigel K H Slater
Nov 28, 2012·Advanced Healthcare Materials·Lei SongDejian Zhou
Jan 27, 2019·Bioengineering & Translational Medicine·William B LiechtyNicholas A Peppas

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