Targeted therapy of colon cancer with aptamer-functionalized albumin nanoparticles loaded with disulfiram.

Chemotherapy remains the primary treatment for most patients with metastatic colorectal cancer (mCRC), yet its efficacy is often limited by severe adverse effects. Drug repurposing offers a promising strategy to accelerate oncology drug development. Disulfiram (DSF), a licensed anti-alcoholism agent, has demonstrated broad-spectrum anticancer activity in preclinical models. However, its clinical translation for oncology is hindered by poor aqueous solubility, rapid metabolism, and lack of tumor selectivity. To overcome these limitations, we developed a novel targeted drug delivery system (Apt-NPs-DSF) by encapsulating disulfiram (DSF) within albumin nanoparticles (NPs) functionalized with the nucleolin-targeting AS1411 aptamer. Apt-NPs-DSF had an average size of 96.4 ± 7.4 nm and was negatively charged with a zeta potential of -19.1 ± 2.2 mV. Furthermore, DSF was released from the albumin NPs with a typical sustained release profile. Apt-NPs-DSF demonstrated favorable serum stability and hemocompatibility. Of note, aptamer-guided NPs were preferentially internalized by nucleolin-expressing CT26 colon cancer cells vs control cells. Moreover, in vitro cytotoxicity assay revealed that Apt-NPs-DSF significantly enhanced the killing of CT26 colon cancer cells. Importantly, in vivo study confirmed that Apt-NPs-DSF achieved superior antitumor efficacy without raising systemic toxicity, outperforming non-targeted counterparts. Collectively, these results suggest that Apt-NPs-DSF has potential in the targeted treatment of colon cancer.