Curcumin-silk tyrosine crosslinked hydrogels

Systemic chemotherapy is still the first-line treatment for cancer, and it’s associated with toxic side effects, chemoresistance and ultimately cancer recurrence. Rapid gelling hydrogels can overcome this limitation by providing localized delivery of anti-cancer agents to solid tumors. Silk hydrogels are extremely biocompatible and suitable for anticancer drug delivery, but faster gelling formulations are needed. In this study, we introduce a rapid gelling hydrogel formulation (< 3 minutes gelling time) due to chemical crosslinking between silk fibroin and curcumin, initiated by the addition of minute quantities of HRP and H ₂ O ₂ . The novel observation in this study is that curcumin, while being a free-radical scavenger, also participates in accelerating silk di-tyrosine crosslinking in the presence of HRP and H ₂ O ₂ . Using UV-Vis, rheology and time-lapse videos, we convincingly show that curcumin accelerates silk di-tyrosine crosslinking reaction in a concentration-dependent manner, and curcumin remains entrapped in the hydrogel post-crosslinking. FTIR results show an increase in secondary beta-sheet structures within hydrogels, with increasing concentrations of curcumin. Furthermore, we show that curcu-min-silk di-tyrosine hydrogels are toxic to U2OS osteosarcoma cells, and most cancer cells are dead within short time scales of 4 hours post-encapsulation.