Polymer-Based Bioorthogonal Nanocatalysts for the Treatment of Bacterial Biofilms

Abstract

Bioorthogonal catalysis offers a unique strategy to modulate biological processes through the in situ generation of therapeutic agents. However, the direct application of bioorthogonal transition metal catalysts (TMCs) in complex media poses numerous challenges due to issues of limited biocompatibility, poor water solubility, and catalyst deactivation in biological environments. We report here the creation of catalytic "polyzymes", comprised of self-assembled polymer nanoparticles engineered to encapsulate lipophilic TMCs. The incorporation of catalysts into these nanoparticle scaffolds creates water-soluble constructs that provide a protective environment for the catalyst. The potential therapeutic utility of these nanozymes was demonstrated through antimicrobial studies in which a cationic nanozyme was able to penetrate into biofilms and eradicate embedded bacteria through the bioorthogonal activation of a proantibiotic.

Transition Metal‐Promoted Reactions in Aqueous Media and Biological Settings

“…The high antimicrobiala ctivity is achieved at concentrations that do not compromise the fibroblast cell viability. [134]…”

“…Accordingly, these nanosystems exhibited excellent catalytic efficiency for the activation of fluoroquinolone prodrugs such as pro‐moxifloxacin or pro‐ciprofloxacin within biofilms of E. coli or Pseudomonas aeruginosa . The high antimicrobial activity is achieved at concentrations that do not compromise the fibroblast cell viability [134] …”

Engineering the Interface between Inorganic Nanoparticles and Biological Systems through Ligand Design

“…Another common stimulus to trigger nanoparticle aggregation is pH, a property can be used to target acidic microenvironments such as those found in tumors or bacterial biofilms [ 125 , 126 , 127 , 128 ]. Early work by Kim demonstrated that nanoparticles can respond to pH changes and form aggregates [ 129 ].…”

Intracellular Activation of Anticancer Therapeutics Using Polymeric Bioorthogonal Nanocatalysts

“…We report here the fabrication of a ruthenium‐based “polyzyme” employing a poly(oxanorbornene imide) scaffold [ 48 ] for in vitro anti‐cancer demonstration. The polymeric scaffolds employed feature cationic hydrophobic imide functionalization, imparting both water solubility and inducing polymer self‐assembly around the ruthenium TMCs.…”