Anti-Trop2 antibody-conjugated bioreducible nanoparticles for targeted triple negative breast cancer therapy

Abstract

Trop2, a transmembrane glycoprotein, has emerged as a biomarker for targeted cancer therapy since it is overexpressed in 80% of triple negative breast cancer (TNBC) patients. For the site-specific delivery of the anticancer drug into TNBC, anti-Trop2 antibody-conjugated nanoparticles (ST-NPs) were prepared as the potential nanocarrier, composed of carboxymethyl dextran (CMD) derivatives with bioreducible disulfide bonds. Owing to its amphiphilicity, the CMD derivatives were self-assembled into nano-sized particles in an aqueous condition. Doxorubicin (DOX), chosen as a model anticancer drug, was effectively encapsulated into the nanoparticles. DOX-loaded ST-NPs (DOX-ST-NPs) rapidly released DOX in the presence of 10mM glutathione (GSH), whereas the DOX release is significantly retarded in the physiological condition (PBS, pH 7.4). Confocal microscopic images and flow cytometry analysis demonstrated that DOX-ST-NPs were selectively taken up by MDA-MB-231 as the representative Trop2-expressing TNBC cells. Consequently, DOX-ST-NPs exhibited higher toxicity to Trop2-positive MDA-MB-231 cancer cells, compared to DOX-loaded control nanoparticles without the disulfide bond or anti-Trop2 antibody. Overall, ST-NPs might be a promising carrier of DOX for targeted TNBC therapy.