A Synthetic, Transiently Thermoresponsive Homopolymer with UCST Behaviour within a Physiologically Relevant Window

Abstract

Interactive materials that can respond to atrigger by changing their morphology,b ut that can also gradually degrade into af ully soluble state,a re attractive building blocks for the next generation of biomaterials.H erein, we design such transiently responsive polymers that exhibit UCST behaviour while gradually losing this property in response to ahydrolysis reaction in the polymer side chains.The polymers operate within ap hysiologically relevant window in terms of temperature,p H, and ionic strength. Whereas such behaviour has been reported earlier for LCST systems,i ti sa tp resent unexplored for UCST polymers.Furthermore,wedemonstrate that, in contrast to LCST polymers,i na queous medium the UCST polymer forms ac oacervate phase belowt he UCST, which can entrap ah ydrophilic model protein, as well as ah ydrophobic dye.B ecause of their non-toxicity,w ea lso provideinvivo proof of concept of the use of this coacervate as aprotein depot, in view of sustained-release applications.Stimuli-responsive polymers,a lso called "smart polymers", respond to chemical or physical changes by ac hange in solution behaviour. [1][2][3] This unique property has fuelled interest in these materials for an umber of applications, including biomaterials design, separation, catalysis,a nd sensors. [4][5][6][7][8][9] Amongst the most intensively studied stimuliresponsive polymers are those that exhibit lower critical solution temperature (LCST) behaviour. [10,11] Such polymers

Recent Advances in Complex Coacervation Design from Macromolecular Assemblies and Emerging Applications

“…[ 78 ] For example, Zhang et al. [ 79 ] synthesized thermoresponsive polymer poly( N ‐(2‐hydroxypropyl)methacrylamide‐glycolamide) (poly(HPMA‐GA)) showing UCST behavior ( Figure a). At a lower temperature, hydrogen bonding of polymer–polymer and hydrophobic interaction drive the coacervation.…”

“…Reproduced with permission. [ 79 ] Copyright 2019, Wiley‐VCH. b) Schematic representation of temperature‐dependent phase behavior of PolyU/spermine.…”

“…Zhang et al. [ 79 ] synthesized a UCST‐type polymer by functionalizing side group of poly( N ‐(2‐hydroxypropyl)methacrylamide) with glycolamide, which formed coacervate at decreasing temperature from 50 °C to room temperature. The phase separation is driven by intra‐ and intermolecular hydrogen bonding between multiple amide and carbonate ester moieties in the polymer repeating units, while hydrophilic model protein BSA could be accommodated after coacervation with no need for simultaneous heating, lowering the danger of thermal denaturation.…”

Synthesis of Thermoresponsive Copolymers with Tunable UCST‐Type Phase Transition Using Aqueous Photo‐RAFT Polymerization

“…[ 11–21 ] The non‐ionic polymers have attracted a great deal of attention due to their insensitivity to salts, which make them more attractive for applications in physiological environment. [ 22–24 ] During the last decade, efforts have been focused toward developing novel water‐soluble copolymers exhibiting UCST behavior by copolymerizing H‐donor monomers ( N ‐acryloyl glycinamide [ 11–16 ] or acrylamide [ 15,17–21,25 ] ) and H‐acceptor monomers (acrylonitrile, [ 11,15,18,19,21,25,26 ] styrene, [ 15,17 ] and butyl acrylate [ 15 ] ). Such (co)polymers have been mainly prepared using free radical polymerization [ 11,14–17,26 ] and by thermally initiated controlled radical polymerization such as atom transfer radical polymerization [ 13 ] and reversible addition fragmentation chain transfer (RAFT) [ 11,12,16–19,25 ] The impacts of various parameters on the UCST phase transition, including salts, pH, molecular weight, molecular weight distribution, and chemical composition, have been well evaluated.…”

Macromolecular Isomerism in Giant Molecules

“…It also helps illustrate the structural evolution pathways of those spherically packed phases. [24] Introduction of spherical C 60 at the end position or mid-position of the rodlike OF motifs yields semiconducting isomeric C 60 -oligofluorene conjugates.D epending on the tethering location, these isomeric giant molecules exhibit distinct morphologies, whichi s critically relatedt ot heir charget ransport properties (Figure 6a). [25] To revealthe effect of the linkingp ositionons elf-assembled structures, Cheng and co-workers systematically varied the linker structure of DPOSS-4BPOSS (Figure 6b).…”