Title : NIR-degradable and biocompatible hydrogels derived from hyaluronic acid and coumarin for drug delivery and bio-imaging
Abstract:
In this work, bioorthogonal and photodegradable hydrogels derived from norbornene (Nb) functionalized hyaluronic acid and a water soluble coumarin-based cross-linker possessing terminal tetrazine (Tz) groups, were developed for NIR-responsive release of doxorubicin (DOX). The inverse electron demand Diels–Alder crosslinking reaction between Nb and Tz functionalities formed the hydrogels at physiological conditions, whereas N2 gas liberated during the reaction created pores in the hydrogels. The gelation time ranges (about 5–20 min) and the viscoelastic behavior (G' ~ 346–1380 Pa) demonstrated that the resulting hydrogels were injectable and possessed tunable mechanical properties. Moreover, hydrogels released the encapsulated DOX upon NIR irradiation, owing to the NIR-responsive cleavage of coumarin-ester, and consequently, induced anti-tumor activity in BT-20 cancer cells. Additionally, the hydrogels could be excited at various wavelengths of the visible spectrum and can emit green to red fluorescence, demonstrating their simultaneous photo-responsive drug release and bioimaging applications. The novel NIR–responsive hydrogels derived from HA and coumarin-based cross-linker, could be auspicious carriers for on demand drug release and bio-imaging applications.