Sivanand S. Pennadam

Stimuli responsive polymers for biomedical applications

Polymers that can respond to external stimuli are of great interest in medicine, especially as controlled drug release vehicles. In this critical review, we consider the types of stimulus response used in therapeutic applications and the main classes of responsive materials developed to date. Particular emphasis is placed on the wide-ranging possibilities for the biomedical use of these polymers, ranging from drug delivery systems and cell adhesion mediators to controllers of enzyme function and gene expression (134 references).

Protein-polymer nano-machines. Towards synthetic control of biological processes

The exploitation of natures machinery at length scales below the dimensions of a cell is an exciting challenge for biologists, chemists and physicists, while advances in our understanding of these biological motifs are now providing an opportunity to develop real single molecule devices for technological applications. Single molecule studies are already well advanced and biological molecular motors are being used to guide the design of nano-scale machines. However, controlling the specific functions of these devices in biological systems under changing conditions is difficult. In this review we describe the principles underlying the development of a molecular motor with numerous potential applications in nanotechnology and the use of specific synthetic polymers as prototypic molecular switches for control of the motor function. The molecular motor is a derivative of a TypeI Restriction-Modification (R-M) enzyme and the synthetic polymer is drawn from the class of materials that exhibit a temperature-dependent phase transition.The potential exploitation of single molecules as functional devices has been heralded as the dawn of new era in biotechnology and medicine. It is not surprising, therefore, that the efforts of numerous multidisciplinary teams [1, 2]. have been focused in attempts to develop these systems. as machines capable of functioning at the low sub-micron and nanometre length-scales [3]. However, one of the obstacles for the practical application of single molecule devices is the lack of functional control methods in biological media, under changing conditions. In this review we describe the conceptual basis for a molecular motor (a derivative of a TypeI Restriction-Modification enzyme) with numerous potential applications in nanotechnology and the use of specific synthetic polymers as prototypic molecular switches for controlling the motor function [4].

Enhanced gene expression through temperature profile-induced variations in molecular architecture of thermoresponsive polymer vectors

Successful non‐viral gene targeting requires vectors to meet two conflicting needs—strong binding to protect the genetic material during transit and weak binding at the target site to enable release. Responsive polymers could fulfil such requirements through the switching of states, e.g. the chain‐extended coil to chain‐collapsed globule phase transition that occurs at a lower critical solution temperature (LCST), in order to transport nucleic acid in one polymer state and release it in another.

Physicochemical characterization of thermoresponsive Poly(N-isopropylacrylamide)-poly(ethylene imine) graft copolymers

Synthetic polycations have shown promise as gene delivery vehicles but suffer from an unacceptable toxicity and low transfection efficiency. Novel architectures are being explored to increase transfection efficiency, including copolymers with a thermoresponsive character. The physicochemical characterization of a family of copolymers comprising a core of the cationic polymer poly(ethylene imine) (PEI) with differing thermoresponsive poly( N-isopropylacrylamide) (PNIPAM) grafts has been carried out using pulsed-gradient spin-echo NMR (PGSE-NMR) and small-angle neutron scattering (SANS). For the copolymers that have longer chain PNIPAM grafts, there is clear evidence of the collapse of the grafts with increasing temperature and the associated emergence of an attractive interpolymer interaction. These facets depend on the number of PNIPAM grafts attached to the PEI core. While a collapse in the smaller PNIPAM grafts is observed for the third polymer, there is no appearance of the interpolymer attractive interaction. These observations provide further insight into the association behavior of these copolymers, which is fundamental to developing a full understanding of how they interact with nucleic acids. Furthermore, the differing behaviors of the three copolymers over temperatures in which the PNIPAM blocks undergo coil-to-globule transitions is indicative of changes in the presentation of charged-core and hydrophobic chain components, which are key factors affecting nucleic acid binding and, ultimately, cell transfection ability.

‘Isothermal’ phase transitions and supramolecular architecture changes in thermoresponsive polymers via acid-labile side-chains

Polymers designed to change their conformation via a phase transition triggered by acidic cleavage of a hydrophobic side-chain have been synthesized and characterised. The new materials were prepared by co-polymerising N-isopropylacrylamide with an acetal-containing pH-sensitive monomer N-(2-(2,4,6-trimethoxyphenyl)-1,3-dioxan-5-yl)acrylamide (TMPDA) and then grafting the resultant linear co-polymers to branched poly(ethyleneimine). The final three-component polycations exhibited Lower Critical Solution Temperature (LCST) behaviour. The structures of these polymers, their solution behaviour and their self-association were characterized by DLS and TEM in water and buffer solutions. The acid-triggered hydrolysis of trimethoxybenzeneacetal side-chains on the poly(N-isopropylacrylamide-co-TMPDA) grafts resulted in changes in lower critical solution temperatures and in solution self-assembly; thus in effect creating an ‘isothermal’ phase transition. The changes in polymer conformation, at acidity levels corresponding to those in cell endosomes, offer promise for these polymers to act as controlled release materials.