gelatin-doxorubicin conjugate

The gelatin-doxorubicin conjugate (G-DOX) is a preclinical macromolecular polymer-drug conjugate developed by researchers at the University of the Sciences in Philadelphia (which merged into Saint Joseph's University in 2022). It consists of the potent anthracycline chemotherapeutic doxorubicin covalently linked to a high-molecular-weight, biodegradable gelatin carrier via a glycylglycine spacer and an acid-labile hydrazone bond. G-DOX is designed to exploit the enhanced permeability and retention (EPR) effect for passive targeting of solid tumors, avoiding renal clearance due to its high molecular weight. Upon accumulation in the tumor microenvironment, the gelatin carrier is degraded by metalloproteinases (such as cathepsin B), facilitating endocytosis. Within the acidic lysosomal compartment, the hydrazone bond is cleaved to release active doxorubicin, thereby inducing localized cytotoxicity and DNA damage while potentially reducing the systemic cardiotoxicity associated with free doxorubicin. It has been evaluated in vitro against breast cancer (including triple-negative breast cancer), prostate cancer, and lymphoma models.

Other names

G-DOXGDOXgelatin-doxorubicin