Enhanced Anticancer Activity in HR +/HER2 + Breast Cancer Cells Using Trastuzumab-Conjugated Liposomes co-loaded with siRNA and Tamoxifen

HR + /HER2 + breast cancer is characterized by the overexpression of hormone receptors (estrogen and progesterone) and the HER2 receptor, leading to aggressive tumor growth and poor prognosis. Conventional treatments often face challenges such as drug resistance and systemic toxicity. This study aims to develop and evaluate trastuzumab-functionalized siRNA and tamoxifen-loaded liposomes (TMX-FL) for targeted therapy in HR + /HER2 + breast cancer. Liposomes were prepared using the thin-film hydration. Surface morphology was analyzed using scanning electron microscopy, while drug release profiles and serum stability of siRNA were assessed. In vitro cytotoxicity, cellular uptake, and Western blot analyses were conducted using HR + /HER2 + (BT474) breast cancer cells. Optimized trastuzumab-conjugated liposomes exhibited a particle size of 97.17 ± 0.2 nm, a zeta potential of 16.93 ± 0.25 mV, and high entrapment efficiencies for tamoxifen (79.02 ± 0.46%) and siRNA (79.85 ± 0.14%). Scanning electron microscopy confirmed spherical morphology. Drug release studies indicated controlled and sustained release, enhancing tamoxifen retention and stability. Serum stability tests demonstrated siRNA protection from degradation. In vitro cytotoxicity assays showed superior anticancer activity of TMX-FL compared to non-targeted tamoxifen-loaded stealth liposomes (TMX-SL) and pure tamoxifen. These findings suggest that TMX-FL liposomes offer a promising strategy for targeted cancer therapy, warranting further preclinical in vivo evaluations to confirm their therapeutic potential and safety profile.