Introduction: Triple-negative breast cancer (TNBC) is categorized as an aggressive subtype of breast cancer that expresses EGFR receptors. mTOR siRNA loaded Paclitaxel (PTX) could be the possible way to treat TNBC. Objective: The aim of this study was to develop an efficient drug delivery system for specifically targeting the TNBC cells without affecting normal cells by formulating PTX - loaded PLGA (Poly (lactic-co- glycolic acid) nanoparticle bio-conjugate with mTOR siRNA. Methods: The nanoparticles were synthesized by double emulsification followed by solvent evaporation. The conjugated nanoparticles were characterized by physiochemical properties (size, shape, entrapment efficiency, and release studies) and cancer cell properties (Cytotoxicity, serum stability, siRNA binding efficiency). Results and Discussion: The prepared mTOR-NP showed the size of 257.3 nm and zeta potential of -32.5 ± 9.4 mV and drug release of 87.6% up to 48 hrs. The gel retardation results showed that mTOR siRNA integrity remained the same after conjugation with nanoparticles. Anticancer activity was confirmed by using MDA-MB231 cell-line and the antibody conjugated nanoparticles showed the significant anticancer activity. Conclusion: We are recommending that mTOR siRNA anchored PTX nanoparticles (mTOR NP) may have the ability to target the TNBC cells and improve the therapeutic action and subsidize the side effects of PTX.