EGFR-mTOR siRNA Loaded Immumonanoparticles for Targeted Chemotherapy of Triple Negative Breast Cancer

Background: Triple-Negative Breast Cancer (TNBC) presents a significant clinical challenge due to its aggressive nature and limited therapeutic options. A promising treatment strategy involves targeting Epidermal Growth Factor Receptor (EGFR) signaling and PI3K/Akt/mTOR pathways that are hyperactivated in many breast carcinomas. In our study, we aimed to develop a drug delivery system utilizing Paclitaxel (PTX) bio-conjugated with mammalian Target of Rapamycin (mTOR) small interfering RNA (siRNA) nanoparticles, which were further conjugated with EGFR to specifically target TNBC cells. Materials and Methods: The nanoparticles were synthesized using a precipitation method followed by solvent evaporation. They were characterized for size, shape, entrapment efficiency, and drug release kinetics. Additionally, we assessed their cytotoxicity, migration assay, and siRNA binding efficiency using gel retardation. Results: The results showed that the EGFR-mTOR siRNA-loaded immuno nanoparticles had a mean size of 186.6 nm with a zeta potential of 46.57±12.3 mV and an entrapment efficiency of 76.3±3.6%. Gel retardation assays confirmed the integrity of mTOR post-conjugation with mTOR immuno nanoparticles. The anticancer activity of mTOR immuno nanoparticles was evaluated using MDA-MB231 and MDA-MB468 TNBC cell lines, demonstrating significant cytotoxicity. The antibody-conjugated immuno nanoparticles showed enhanced targeting specificity and efficacy against TNBC cells. Conclusion: In summary, mTOR immuno nanoparticles exhibit potential as a targeted therapeutic strategy for TNBC, providing enhanced effectiveness while reducing the adverse effects associated with conventional chemotherapy. This novel drug delivery system's potential to improve therapeutic efficacy and mitigate systemic toxicity underscores its translational relevance in cancer treatment.