Abstract
Poly(2-oxazoline)s (POx) are an attractive platform for the development of non-viral gene delivery systems. The combination of POx moieties, exhibiting excellent biocompatibility, with DNA-binding polyethyleneimine (PEI) moieties into a single copolymer chain is a promising approach to balance toxicity and transfection efficiency. The versatility of POx in terms of type of substituent, copolymer composition, degree of polymerization, degree of hydrolysis, and chain architecture, as well as the introduction of stimuli-responsive properties, provides opportunities to finely tune the copolymer characteristics and physicochemical properties of the polyplexes to increase the biological performance. An overview of the current state of research in the POx–PEI-based gene delivery systems focusing particularly on thermosensitive POx is presented in this paper.
Highlights
Gene therapy refers to the treatment of acquired and hereditary genetic diseases by modifying and repairing the genetic structure [1,2,3]
Even for the copolymers of higher degree of hydrolysis (DH), the ζ potential was found to shift to more positive values (Figure 4a), implying that the same events of structural rearrangement upon heating above observed exclusively for PiPOx, which has been rationalized in terms of the facilitation of dipolar interactions between amide groups upon long-term annealing at temperatures above the lower critical solution temperature (LCST)
It is noteworthy that the introduction of ethylene imine units has been found to completely inhibit the high-temperature crystallization of PiPOx [42]. The latter is a specific property observed exclusively for PiPOx, which has been rationalized in terms of the facilitation of dipolar interactions between amide groups upon long-term annealing at temperatures above the LCST leading to an irreversible formation of micron-sized coagulated particles built of nanofibers [44]
Summary
Gene therapy refers to the treatment of acquired and hereditary genetic diseases by modifying and repairing the genetic structure [1,2,3]. An important feature of POx is the unique property of some family members to undergo a reversible soluble-to-insoluble state transition in response to small changes in temperature [28,33] and exhibit a lower critical solution temperature (LCST) in water. The partial hydrolysis is highly desirable, as it leads to copolymers consisting of two different moieties—(i) cationic, pH-responsive, and DNA binding and (ii) non-ionic, water-soluble or exhibiting LCST properties, and biocompatible. This combination of properties seems to be promising and attractive for the development of non-viral vectors, the POx–PEI copolymers are somewhat under-researched. Examples for POx–PEI copolymers derived from POx, which are not thermosensitive, are given to complement the picture and for better understanding of their behavior
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