Real time monitoring of peptide delivery in vitro using high payload pH responsive nanogels†
Nanogels are attractive delivery vehicles for small hydrophilic cargo, such as peptides, but there is a limited understanding of how the structure of both the nanogel and cargo affect the drug loading and release properties, particularly in biological environments. We have used Förster resonance energy transfer (FRET) to study the loading and release behaviour of a series of hydrophilic charged peptides (SNKAY, SNKKY and SNDDY) in a set of pH-responsive methacrylic acid (pMAA) core crosslinked nanogels that were prepared through miniemulsion polymerisation from a PEGMEMA–DMAEMA–tBuMA terblock copoylmer. Our nanogels show an extremely high loading capacity of the positively charged peptides (400–800 wt% in the best cases), absorbing them from solution at pH 7.4 without any need for purification. At pH values below 6, the peptide is rapidly expelled from the nanogel due to the collapse of the core and protonation of the positively charged inner shell. By combining FRET with fluorescence lifetime imaging microscopy (FLIM), we were able to monitor this in vitro and found that most of the drug is released within the first 10 min after cell uptake.
- This article is part of the themed collection: Polymer Chemistry Emerging Investigators