Nanocapsules from metal-phenolic networks for targeted drug delivery

Project Summary

Capsules formed from metal-phenolic coordination networks (MPNs) have emerged as a versatile platform for drug delivery. In 2016, CBNS researchers formed MPN capsules from functional polymers (hyaluronic acid (HA)) to target the CD44 receptor that is overexpressed on certain cancer cells. Interaction between the targeting ligand on the capsule surface and a tumour-specific cell receptor increased cellular association and internalisation.

At the same time, incorporation of a low-fouling polymer (polyethylene glycol (PEG)) into MPN capsules reduced non-specific binding to cells that did not express the receptor, allowing for optimisation of targeting efficiency. Anticancer drugs can be encapsulated into the capsules and released by the pH-responsive nature of the MPNs that disassemble at the slightly acidic intracellular environment pH but remain stable at neutral pH. Drug loaded MPN capsules with an optimised HA/PEG ratio showed higher cytotoxicity to a CD44 overexpressing cancer cell line compared with a cell line with low CD44 expression, demonstrating a potential application for targeted drug delivery.

Notably, the targeting ability of HA- based MPN capsules was maintained in the presence of physiologically relevant proteins that adsorb on nanoparticle surfaces and form a protein corona.