Development of a cationic polyethyleneimine-poly(lactic-co-glycolic acid) nanoparticle system for enhanced intracellular delivery of biologics

Shannon R. Tracey, Peter Smyth, Una M. Herron, James F. Burrows, Andrew J. Porter, Caroline J. Barelle, Christopher J. Scott*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

14 Downloads (Pure)

Abstract

Intracellular delivery of proteins, peptides and biologics is an emerging field which has the potential to provide novel opportunities to target intracellular proteins, previously deemed ‘undruggable’. However, the delivery of proteins intracellularly remains a challenge. Here, we present a cationic nanoparticle delivery system for enhanced cellular delivery of proteins through use of a polyethyleneimine and poly-(lactic-co-glycolic acid) polymer blend. Cationic nanoparticles were shown to provide increased cellular uptake compared to anionic and neutral nanoparticles, successfully delivering Variable New Antigen Receptors (vNARs), entrapped within the nanoparticle core, to the cell interior. vNARs were identified as ideal candidates for nanoparticle entrapment due to their remarkable stability. The optimised 10% PEI-PLGA nanoparticle formulation displayed low toxicity, was uniform in size and possessed appropriate cationic charge to limit cellular toxicity, whilst being capable of escaping the endo/lysosomal system and delivering their cargo to the cytosol. This work demonstrates the ability of cationic nanoparticles to facilitate intracellular delivery of vNARs, novel biologic agents with potential utility towards intracellular targets.

Original languageEnglish
Pages (from-to)33721-33735
Number of pages15
JournalRSC Advances
Volume13
Issue number48
Early online date17 Nov 2023
DOIs
Publication statusEarly online date - 17 Nov 2023

Keywords

  • General Chemical Engineering
  • General Chemistry

Fingerprint

Dive into the research topics of 'Development of a cationic polyethyleneimine-poly(lactic-co-glycolic acid) nanoparticle system for enhanced intracellular delivery of biologics'. Together they form a unique fingerprint.

Cite this