Photo-triggerable hydrogel–nanoparticle hybrid scaffolds for remotely controlled drug delivery

Abstract

Remotely-triggerable drug delivery systems enable the user to adjust dosing regimens on-demand based on a patient's physiological response and clinical needs. However, currently reported systems are limited by the non-specific leakage of drugs in the absence of triggering and the lack of repeatability over multiple cycles of release. To this end, we have designed a unique hydrogel–nanoparticle hybrid scaffold that provides a chemically-defined, remotely-triggerable and on-demand release of small molecule drugs. Our hybrid platform consists of three distinct components: (1) a photo-triggerable chemical compound, which serves to release a covalently-bound drug upon photo-irradiation, (2) a nanoparticle, which serves to covalently bind the photo-triggerable compound, and (3) a polymeric hydrogel, which serves to hold the drug-conjugated nanoparticle. Upon photo-irradiation, the activation of the photo-triggerable compound is designed to initiate a series of intramolecular chemical rearrangements, which would cleave the covalently-bound drug and release it from the hydrogel. The combination of these distinct components in a single scaffold proved to be an effective drug delivery system, as demonstrated by the delivery of a model drug to a malignant cancer line. Our hybrid scaffold can be easily tuned for practically any biological application of interest, thus offering immense potential for clinical therapies.