Hydrogel-based platforms for site-specific doxorubicin release in cancer therapy

Hydrogels are promising candidates for the delivery of therapeutics in the treatment of human cancers. Regarding to the biocomaptiiblity, high drug and encapsulation efficacy and adjustable physico-chemical features, the hydrogels have been widely utilized for the delivery of chemotherapy drugs. Doxorubicin (DOX) is one of the most common chemotherapy drugs used in cancer therapy through impairing topoisomerase II function and increasing oxidative damage. However, the tumor cells have developed resistance into DOX-mediated cytotoxic impacts, requiring the delivery systems to increase internalization and anti-cancer activity of this drug. The hydrogels can deliver DOX in a sustained manner to maximize its anti-cancer activity, improving cancer elimination and reduction in side effects and drug resistance. The natural-based hydrogels such as chitosan, alginate and gelatin hydrogels have shown favourable biocompatibility and degradability in DOX delivery for tumor suppression. The hydrogels are able to co-deliver DOX with other drugs or genes to enhance drug sensitivity and mediate polychemotherapy, synergistically suppressing cancer progression. The incorporation of nanoparticles in the structure of hydrogels can improve the sustained release of DOX and enhancing intracellular internalization, accelerating DOX's cytotoxicity. Furthermore, the stimuli-responsive hydrogels including pH-, redox- and thermo-sensitive platforms are able to improve the specific release of DOX at the tumor site. The DOX-loaded hydrogels can be further employed in the clinic for the treatment of cancer patients and improving efficacy of chemotherapy.