Novel drug-loaded nano-polymer comparison: amoxicillin between ceftriaxone for MCF-7 breast cancer cytotoxicity.

The rising challenges of conventional chemotherapy, including drug resistance and systemic toxicity, necessitate the exploration of novel therapeutic strategies. Repurposing existing antibiotics offers a promising, cost-effective approach in oncology. In this study, we investigate the anticancer potential of two common β-lactam antibiotics, amoxicillin and ceftriaxone, by conjugating them to a novel glycerol-phthalic anhydride nano-polymer. Successful conjugation and nanoscale formulation (∼97 nm) were confirmed through FT-IR, NMR, and DLS. When evaluated against aggressive MCF-7 breast cancer cells, the ceftriaxone conjugate demonstrated superior efficacy, showing 14% greater cytotoxicity (IC50 = 38.52 vs. 44.8 µg/mL) and inducing extensive apoptosis, evidenced by membrane blebbing and nuclear fragmentation. Molecular docking revealed a mechanistic basis for this enhanced activity, with ceftriaxone forming stronger binding interactions (-7.8 kcal/mol) with key breast cancer proteins, including π-sulfur and hydrogen bonds. This work establishes a scalable nano-polymer platform for antibiotic repurpose, identifies ceftriaxone as a superior candidate for breast cancer therapy, and provides a critical mechanistic bridge between drug chemistry and tumor biology. With its established clinical safety, this ceftriaxone-based system represents a viable candidate for rapid translation to in vivo studies.