Biosensitive hydrogel depot with rapid and long-term drug delivery efficacy

Anti-cancer therapeutics need to be well protected by a carrier and highly targeted to the tumor site. Ideally, the release of therapeutics from the cargo should be sustained to provide long-term efficacy, however, once entering the cancer cells, drug release to the cytoplasm should be immediate to rapidly kill cancer cells^[1]. To reach this goal, we designed nanoparticle-crosslinked hydrogel patch with two distinct release kinetics. The therapeutic payload is slowly deployed over time while being locally delivered to the tumor in a highly selective manner, however, following cellular uptake of the dual sensitive nanoparticles, both pH^[2] and redox^[3,4] sensitive particles, impart rapid drug release to ensure effective cancer abrogation. The device is embedded with biosensitive nanogels that are locally released to the tumor tissue in a sustained manner by their sustained release from the hydrogel scaffold. Nanogels selectively uptaken by cancer cells rapidly disassemble by the redox and PH triggers to release the anti-cancer therapeutics.