Abstract
Purpose: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer that lacks targeted therapies, making its treatment highly challenging. This study aimed to design a novel dual-targeted drug delivery system to improve therapeutic efficacy and reduce the side effects of conventional chemotherapy. Methods: Solid lipid nanoparticles (SLNs) were synthesized using a double emulsion solvent evaporation method to encapsulate doxorubicin. These SLNs were then covalently conjugated with a diabody targeting both epidermal growth factor receptor (EGFR) and CD44, which are overexpressed in TNBC cells. The resulting nanoparticles were characterized in terms of size, morphology, zeta potential, and encapsulation efficiency. In vitro cytotoxicity was assessed using MDA-MB-468 TNBC cells. Results: The optimized dual-targeted SLNs exhibited appropriate size (~116 nm), high encapsulation efficiency (~79%), and good stability. In vitro assays demonstrated that diabody-conjugated SLNs significantly enhanced cellular uptake and cytotoxicity compared to both free doxorubicin and untargeted SLNs, particularly at higher concentrations. Conclusion: The results support the potential of diabody-conjugated SLNs as an effective and selective drug delivery system for TNBC. This approach offers improved therapeutic outcomes and reduced systemic toxicity, suggesting its promise for future clinical applications in targeted breast cancer therapy.