Hydrogen Bonding-Driven Self-Coacervation of Nonionic Homopolymers for Stimuli-Triggered Therapeutic Release.

Inspired by the unique functionalities of biomolecular membraneless organelles (MLOs) formed via liquid-liquid phase separation (LLPS) of intrinsically disordered proteins (IDPs) and nucleic acids, a great deal of effort has been devoted to devising phase-separated artificial subcellular dynamic compartments. These endeavors aim to unravel the molecular mechanism underlying the formation and intracellular delivery of susceptible macromolecular therapeutics. We report herein pyroglutamic acid (PGA)-based well-defined homopolymers featuring stimuli-tunable reversible self-coacervation ability. The polymer exhibits an upper critical solution temperature (UCST) transition in aqueous solutions and has the propensity to undergo cooling-induced LLPS, producing micrometer-sized liquid droplets. This phase separation phenomenon could be modulated by various factors, including polymer concentration, chain length, solution pH, and types and concentrations of different additives. These micrometer droplets are thermally reversible and encapsulate a wide variety of cargoes, including small hydrophobic fluorescent molecules, hydrophilic anticancer drugs, and fluorophore-labeled macromolecular proteins (bovine serum albumin and lysozyme). The payloads were released by exploiting the thermo/pH-mediated disassembly behavior of the coacervates, preserving the bioactivity of the sensitive therapeutics. This environmentally responsive, simple yet versatile artificial MLO model system will provide insights into the biomolecular nonionic condensates and pave the way for the de novo design of dynamic biomolecule depots.

Inhibition and eradication of bacterial biofilm using polymeric materials.

Biofilms, ubiquitous in nature, are three-dimensional complex microbial communities sheathed in a self-secreted extracellular polymeric matrix. Infections caused by these communities have sprouted as serious threats to global healthcare systems due to their intrinsic tolerance toward conventional antibiotics. There is a huge demand for alternative "cutting-edge" materials featuring strong antibiofilm abilities to mitigate and/or exterminate pre-matured biofilms. Natural or synthetic macromolecule-based compounds have evolved as one of the most sought-after materials because of their unique stimulus-directed selective targeting efficiency to the bacterial cell, antibiotic-encapsulation ability endowing them with a synergistic effect, and highly dense embedded cationic functionalities that promote accumulation within the biofilm. In this comprehensive review, we aim to highlight the progress made in inhibiting or eradicating bacterial biofilms using various forms of polymeric material including cationic and charge-switchable macromolecules, conjugated polymers, polymeric metal nanocomposites, hydrogels, and supramolecular polymers. We particularly emphasize understanding the underlying antibiofilm mechanisms of each presented example ushered in by state-of-the-art synthetic strategies. Lastly, focusing on bench-to-bedside, the review is concluded by providing some forthcoming aspects and possible future development directions to expand polymer-based antibiofilm research, keeping their clinical translations in mind.

Stimuli-Responsive Aggregation-Induced Emission (AIE)-Active Polymers for Biomedical Applications.

At high concentration or in the aggregated state, most of the traditional luminophores suffer from the general aggregation-caused quenching (ACQ) effect, which significantly limits their biomedical applications. On the contrary, a few fluorophores exhibit an aggregation-induced emission (AIE) feature which is just the opposite of ACQ. The luminophores with aggregation-induced emission (AIEgens) have exhibited noteworthy advantages to get tunable emission, excellent photostability, and biocompatibility. Incorporating AIEgens into polymer design has yielded diversified polymer systems with fascinating photophysical characteristics. Again, stimuli-responsive polymers are capable of undergoing chemical and/or physical property changes on receiving signals from single or multiple stimuli. The combination of the AIE property and stimuli responses in a single polymer platform provides a feasible and effective strategy for the development of smart polymers with promising biomedical applications. Herein, the advancements in stimuli-responsive polymers with AIE characteristics for biomedical applications are summarized. AIE-active polymers are first categorized into conventional π-π conjugated and nonconventional fluorophore systems and then subdivided based on various stimuli, such as pH, redox, enzyme, reactive oxygen species (ROS), and temperature. In each section, the design strategies of the smart polymers and their biomedical applications, including bioimaging, cancer theranostics, gene delivery, and antimicrobial examples, are introduced. The current challenges and future perspectives of this field are also stated at the end of this review article.