Grafting strategies for the synthesis of active DNase I polymer biohybrids

Enlightening advances in polymer bioconjugate chemistry: light-based techniques for grafting to and from biomacromolecules

“…As exciting as these advances are, there are some biomacromolecules whose sensitivity to copper precludes them from participating in bioconjugation reactions using ATRP. 94 While the development of metal-free photoATRP may be able to address metal catalyst sensitivity in biological systems in the future, [95][96][97][98] RAFT polymerizations are an excellent metal-free alternative for us to explore (vide infra).…”

“…Graing-to reactions offer the benet of decoupling the polymerization chemistry from the oen sensitive biological entity to which the polymer will be attached, providing a more benign attachment strategy for sensitive proteins or polymers. 94 In fact, all of the polymer-protein conjugates that are industrially relevant are synthesized using a graing-to approach. Nonetheless, there are inherent steric constraints on coupling two macromolecules, and in some cases, purication can be challenging.…”

DNase I functional microgels for neutrophil extracellular trap disruption

“…[38][39][40] However, the low serum stability, and fast deactivation by environmental stimuli have been considered as the limiting factors for clinical applications of DNase I. 41 In this work, we show the synthesis of biohybrid, highly hydrophilic microgels conjugated to the DNase I (DNase I MGs) for the digestion of NETs. The systematically studied conjugation of the enzyme to the microgel abstains any influence on the structural stability of the protein.…”

PEGylation of recombinant human deoxyribonuclease I decreases its transport across lung epithelial cells and uptake by macrophages

“…Most markedly, the residence time of PEGylated rhDNase in murine lungs after intratracheal instillation was extended to over 15 days with PEGs of 30 kDa and 40 kDa compared with less than 24 h for native rhDNase [7]. PEGylation of rhDNase was also reported to enhance its thermal stability [17]. Reduced systemic absorption, mucoadhesion, decreased uptake by respiratory cells, and protection against degradation in the lungs are the main mechanisms evoked to explain the longer retention of PEGylated proteins [18].…”