Investigating histidinylated highly branched poly(lysine) for siRNA delivery

Abstract

Here we examined how histidinylation of branched poly-l-lysine impacts delivery efficiency and toxicity of siRNA delivery in glioblastoma cells.

Polysarcosine functionalised cationic polyesters efficiently deliver self-amplifying mRNA

“…S2 and Table S1†). Specifically looking at the range related to endosomal acidification, considered between pH 7.4 and pH 5.0, 39 PEI displayed a buffering capacity 12 mol of H + per mol of ionisable nitrogen in this pH range, whilst OH-(pBDD-5AP)-OH and pSar-(pBDD-5AP)-pSar displayed buffering capacities of 4.0 and 3.5 respectively. The weaker buffering capacities observed for the PBAEs, compared to a branched PEI control, was likely due to PEI's structure containing a high density of primary, secondary and tertiary amines compared to our PBAEs only exhibiting tertiary amines at a reduced density across the polymer chain.…”

Advances in non-viral mRNA delivery to the spleen

“…Alazzo and colleagues histidinylated branched poly(lysine) and achieved higher transfection efficiency and biocompatibility of histdinylated poly(lysine) nanoparticles as compared to unmodified poly(lysine) nanoparticles. 139 Additionally, Dirisala et al synthesized a poly(lysine) and poly( l -ornithine) co-polymer bridged by a methylene spacer. Encapsulation of mRNA using this co-polymer showed higher stability against nucleases and better overall transfection and endosomal escape in vitro (Fig.…”

Charge neutralized poly(β-amino ester) polyplex nanoparticles for delivery of self-amplifying RNA

“…16 Polymeric vectors have potential as alternatives to lipids for RNA delivery owing to their wide chemical diversity, formulation exibility, range of functional groups for targeting, stability in polyplex form, and well-established manufacturing processes. 17 Indeed, many different cationic polymers have been used as non-viral polymeric vectors for RNA delivery, including poly(ethyleneimine), 18 poly(lysine), 19 chitosan, 20 polyamidoamines 21 and poly(baminoesters). 22 Although polymer-RNA complexes are widely established in this eld, the high positive charge density of these materials means that there are toxicity concerns potentially limiting clinical applications.…”