Cetuximab-conjugated sodium selenite nanoparticles for doxorubicin targeted delivery against MCF-7 breast cancer cells.

Aim: To develop and characterize doxorubicin-loaded sodium selenite nanoparticles (SSNP-DOX) and their surface attachment with cetuximab (mAb-SSNP-DOX). Methods: SSNP-DOX was formulated by gelation and then conjugated with cetuximab to form mAb-SSNP-DOX. Characterization included DLS, SEM, TEM, DSC, Raman spectroscopy and XRD. In vitro, the kinetics of doxorubicin release and cytotoxicity in MCF-7 breast cancer cells were investigated. Results: The zeta potential for SSNP-DOX and mAb-SSNP-DOX was -14.4 ± 10.1 mV and -27.5 ± 7.28 mV, with particle sizes of 181.3 nm and 227.5 nm, respectively. The formulation intensity was 89.7% for SSNP-DOX and 100% for mAb-SSNP-DOX, with PDI values of 0.419 and 0.251, respectively. SEM and TEM showed that mAb-SSNP-DOX was smooth and spherical. The DSC analysis revealed exothermic peaks at 102.44°C for SSNP-DOX and 144.21°C for mAb-SSNP-DOX, along with endothermic peaks at 269.19°C and 241.6°C, respectively. Raman spectroscopy showed a higher intensity for mAb-SSNP-DOX. The XRD study showed different peaks for each formulation. Both followed zero order kinetics for doxorubicin release. Cytotoxicity studies showed significant effects and high apoptosis in MCF-7 cells for both formulations. Conclusion: The mAb-SSNP-DOX showed promising properties, more effective doxorubicin release and higher cytotoxicity against breast cancer cells compared with SSNP-DOX. Article highlights Breast cancer Breast cancer is a significant cause of morbidity and mortality worldwide and is characterized by high heterogeneity and treatment resistance. MCF-7 cells are a commonly used human breast cancer cell line in research and a model for studying the efficacy of therapeutic interventions. Nanoparticle drug delivery system Drug delivery systems in the form of nanoparticles improve drugs' therapeutic efficacy and stability while minimizing unwanted side effects by enabling precise delivery to cancer cells. Targeted nanoparticle drug delivery systems, such as those incorporating monoclonal antibodies, further improve treatment outcomes by selectively targeting cancer cells and causing less damage to healthy tissue. Targeted breast cancer treatment The study focused on developing injectable nanoparticle formulations, SSNP-DOX and mAb-SSNP-DOX, which effectively target MCF-7 breast cancer cells. Combining cetuximab, a monoclonal antibody targeting the epidermal growth factor receptor (EGFR), with SSNP-DOX improved the specificity and efficacy of the treatment. Characterization & physicochemical stability The nanoparticle formulations were comprehensively characterized using dynamic light scattering (DLS), differential scanning calorimetry (DSC), Raman spectroscopy, x-ray diffraction (XRD) and nuclear magnetic resonance spectroscopy (NMR). These techniques confirmed the formulations' stability and uniformity, ensuring their suitability for targeted drug delivery. In vitro performance & enhanced efficacy The release profiles of doxorubicin from SSNP-DOX and mAb-SSNP-DOX showed sustained drug release over a prolonged period. In vitro, cytotoxicity studies showed that both formulations effectively suppressed the growth of MCF-7 breast cancer cells. Of the two, mAb-SSNP-DOX was the superior formulation, performing better on all parameters tested. Target specificity & overcoming drug resistance mAb-SSNP-DOX showed increased specificity in targeting breast cancer cells due to cetuximab. This combination of nanoparticles with cetuximab represents a promising approach to overcoming drug resistance in the treatment of breast cancer, offering improved efficacy and targeting of breast cancer cells. Future directions Future research should focus on optimizing these formulations, investigating the underlying molecular mechanisms and conducting extensive in vivo studies to validate the therapeutic potential of mAb-SSNP-DOXstance and conducting extensive in vivo studies to validate these findings. [ABSTRACT FROM AUTHOR]