Interactive materials are an emerging class of systems that can offer control over response and adaptivity in polymer structures towards the meso- and macroscale. Here, we use enzyme regulated cleavage of peptide crosslinkers in polymer hydrogels to release a cytotoxic therapeutic nanoparticle with an adaptable mechanism. Hydrogel microplates were formed through polyethylene glycol/peptide photoinitiated thiol-ene chemistry in a soft-lithography process to give square plates of 20 by 20 μm with a height of 10 μm. The peptide was chosen to be degradable in the presence of matrix metalloproteinase 2/9 (MMP-2/9). The hydrogel material's mechanical properties, swelling, and protease degradation were characterised. The microfabricated hydrogels were loaded with docetaxel (DTXL) containing poly(dl-lactide--glycolide) (PLGA) nanoparticles, and characterised for enzyme responsivity, and toxicity to MMP-2/9 overexpressing brain cancer cell line U87-MG. A 5-fold decrease in EC was seen compared to free DTXL, and a 20-fold decrease was seen for the MMP responsive microplates a non-degradable control microplate. Potential applications of this system in post-resection glioblastoma treatment are envisioned.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10540463 | PMC |
| http://dx.doi.org/10.1039/d3lp00057e | DOI Listing |
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