pH-induced size changes in solutions of cholesteric liquid- crystal polymers studied by SANS

2nd Dynamics of Molecules and Materials

物理学;材料科学

Pérez Méndez, Mercedes^1 ; Rodriguez Martinez, Daniel^2,3 ; King, Stephen M.^3

Institute of Polymer Science and Technology, Group of Physical-Chemistry and Modelization of Macromolecules (PCMM), C/ Juan de la Cierva, 3, Madrid

28006, Spain^1

Centro Andaluz de Biología Molecular y Medicina Regenerativa Edif. CABIMER, Avda. Americo Vespucio, s/n, Sevilla

41092, Spain^2

ISIS Facility, STFC Rutherford Appleton Laboratory, Harwell Oxford, Didcot, Oxfordshire

OX11 OQX, United Kingdom^3

关键词: Biomacromolecules;    Buffering capacities;    Membrane activity;    Molecular expansions;    Physiological pH;    Polymer conformation;    Radius of gyration;    Transfection agents;   

Others  :  https://iopscience.iop.org/article/10.1088/1742-6596/554/1/012011/pdf
DOI  :  10.1088/1742-6596/554/1/012011

学科分类：材料科学（综合）

来源: IOP

【 摘 要 】

Polycations possessing substantial buffering capacity below physiological pH, are intrinsically efficient transfection agents. These vectors have been shown to deliver genes as well as oligonucleotides, both in vitro and in vivo, by protecting DNA from inactivation by blood components. Their efficiency relies on extensive endosome swelling and rupture that provides an escape mechanism for the polycation/DNA complexes. Recently, biocompatible cationic cholesteric liquid-crystal polymers (ChLCP) have proved able to condense and successfully transfect DNA, acting as non-viral vectors. Here the radius of gyration of the new ChLCPs is determined by SANS as a function of pH, the ultimate aim being to correlate changes in polymer conformation with membrane activity. With increasing pH the polymers apparent radii of gyration increased to a maximum, before subsequently decreasing. This molecular expansion, on passing from acidic pH environment (cf., lysosome pH 3.5- 4, late endosome pH 5- 6, early endosome pH 6- 6.5) to neutral pH (cytosol pH=7-7.4), matches the endocytic route through the cell, where the pH change is used as a signal to release biomacromolecules, such as DNA. It confirms that the new cationic ChLCPs could act as an endosomolytic release system in gene therapy according to the hypothesis of "the proton sponge".