Royal College of Surgeons in Ireland
Polym Chem 2022-13-654.pdf (1.05 MB)

Exploring the potential of polypeptide–polypeptoide hybrid nanogels for mucosal delivery

Download (1.05 MB)
journal contribution
posted on 2022-11-28, 10:19 authored by Tao XuTao Xu, Dimitrios Skoulas, Dawei Ding, Sally-Ann CryanSally-Ann Cryan, Andreas HeiseAndreas Heise

Amphiphilic nanoparticles with high drug loading capacity and mucus penetration properties are attractive for the delivery of potent hydrophobic drugs across the mucosal barrier in tumor therapy. In this study we report a facile strategy towards biocompatible and tumour microenvironment responsive nanogels, capable of controlling the mucosal delivery and release of a model dye. Polypeptide–polypeptoide hybrid nanogels were obtained by the chain extension of corona-forming poly(sarcosine) with N-carboxyanhydrides (NCA) of phenylalanine and cystine as a core crosslinker. The nanogels exhibited a suitable size range of around 100 nm and a spherical morphology as monitored by dynamic light scattering (DLS), transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). They further showed a reduction-responsive behaviour through the cleavage of the cystine disulfide core crosslinks by glutathione at concentrations present in the intracellular environment as well as a lack of cytotoxicity against both cancerous and non-cancerous cell lines. Lead nanogels facilitated an enhanced transport of a model hydrophobic dye across artificial mucus compared to the dye alone with a reduction sensitive release in the presence of glutathione. This work provides a facile strategy for the synthesis of responsive nanomedicines in anti-cancer therapy where mucosal barriers have to be overcome. 


European Union’s Horizon 2020 research and innovation programme under grant agreement No. 883951




The original article is available at

Published Citation

Xu T, Skoulas D, Ding D, Cyran SA, Heise A. Exploring the potential of polypeptide–polypeptoide hybrid nanogels for mucosal delivery. Polym Chem 2022;13:6054-6060

Publication Date

10 October 2022


  • Amber (Advanced Material & Bioengineering Research) Centre
  • Chemistry
  • CURAM Centre for Research in Medical Devices
  • School of Pharmacy and Biomolecular Sciences
  • Tissue Engineering Research Group (TERG)

Research Area

  • Respiratory Medicine
  • Chemistry and Pharmaceutical Sciences
  • Biomaterials and Regenerative Medicine


Royal Society of Chemistry (RSC)


  • Published Version (Version of Record)