Engineered Polymer-Supported Biorthogonal Nanocatalysts Using Flash Nanoprecipitation

Abstract

Transition-metal catalysts (TMCs) effect bioorthogonal transformations that enable the generation of therapeutic agents in situ, minimizing off-target effects. The encapsulation of insoluble TMCs into polymeric nanoparticles to generate “polyzymes” has vastly expanded their applicability in biological environments by enhancing catalyst solubility and stability. However, commonly used precipitation approaches provide limited encapsulation efficiency in polyzyme fabrication and result in a low catalytic activity. Herein, we report the creation of polyzymes with increased catalyst loading and optimized turnover efficiency using flash nanoprecipitation (FNP). Polyzymes with controlled size and catalyst loading were fabricated by tuning the process conditions of FNP. The biological applicability of polyzymes was demonstrated by efficiently transforming a non-toxic prodrug into the active drug within cancer cells.

Bioorthogonal nanozymes: an emerging strategy for disease therapy

“…The direct usage of naked TMCs in the living environment always raises common concerns, mainly including poor stability, loss of catalytic activity and toxicity to tissues and organs. 70,71 These issues that need to be addressed constitute a major driving force for developing TMC-based bioorthogonal nanozymes, encouraging researchers to design effective strategies that can ameliorate the catalytic properties of TMCs.…”

Amphiphilic polymeric nanoparticles enable homogenous rhodium-catalysed NH insertion reactions in living cells

“…7 Rotello and co-workers have made significant contributions to this field by developing bioorthogonal polyzymes and showing the efficacy of flash nanoprecipitation strategy to increase catalyst loading and turnover frequency. [55][56][57] Previously in our group, Liu et al explored the potential of these nanoparticles to encapsulate Pd(II) and Cu(I) catalysts to perform bond-cleavage reactions in living cells. However, despite the promising results in vitro their catalytic activity was significantly diminished in complex environment due to the presence of deactivating agents.…”

Biodegradable Antibacterial Bioorthogonal Polymeric Nanocatalysts Prepared by Flash Nanoprecipitation

“…Incorporation of hemin into hydrophobic PLA polymers is challenging due to the presence of carboxylic moieties on the hemin structure that reduce the hydrophobicity of the porphyrin. Flash nanoprecipitation (FNP) is a versatile nanoparticle production tool that uses rapid micromixing to create high supersaturation conditions leading to high solute encapsulation efficiency in polymer-based delivery vehicles . We report here the efficient and reproducible generation of PLA–hemin nanocatalysts using FNP.…”

“…Flash nanoprecipitation (FNP) is a versatile nanoparticle production tool that uses rapid micromixing to create high supersaturation conditions leading to high solute encapsulation efficiency in polymer-based delivery vehicles. 42 We report here the efficient and reproducible generation of PLA−hemin nanocatalysts using FNP. PLA backbones were synthesized with both hydrophobic and hydrophilic segments, as required for FNP.…”