Matrix metalloproteinase responsive hydrogel microplates for programmed killing of invasive tumour cells.
Alexander B CookAnnalisa PalangeMichele SchlichElena BellottiSayanti BrahmachariMartina di FrancescoPaolo DecuzziPublished in: RSC applied polymers (2023)
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- co -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 50 was seen compared to free DTXL, and a 20-fold decrease was seen for the MMP responsive microplates versus a non-degradable control microplate. Potential applications of this system in post-resection glioblastoma treatment are envisioned.
Keyphrases
- drug delivery
- cancer therapy
- hyaluronic acid
- wound healing
- drug release
- tissue engineering
- cell migration
- induced apoptosis
- oxidative stress
- body mass index
- cell cycle arrest
- high resolution
- white matter
- squamous cell carcinoma
- papillary thyroid
- transcription factor
- squamous cell
- radiation therapy
- cell proliferation
- multiple sclerosis
- physical activity
- young adults
- signaling pathway
- extracellular matrix
- combination therapy
- cerebral ischemia