Trastuzumab-Conjugated Nanoparticles: Design And Synthesis Of Trastuzumab-Conjugated Nanoparticles For Targeted Delivery Of Chemotherapeutic Agents To Her2-Positive Breast Cancer Cells
Keywords:
Trastuzumab, Nanoparticles, HER2-positive breast cancer, Targeted drug delivery, Docetaxel, PLGA-PEG, pH-sensitive release, Receptor-mediated endocytosis.Abstract
This study developed trastuzumab-conjugated nanoparticles (Tras-NP) for targeted docetaxel delivery to HER2-positive breast cancer cells. Docetaxel-loaded PLGA-PEG-COOH nanoparticles were synthesized via nano-precipitation, forming a monodisperse (~160 nm) core. Trastuzumab was covalently conjugated via EDC/NHS chemistry, confirmed by a size increase to ~172 nm, a zeta potential shift from -28.4 mV to -19.7 mV, and characterization with FTIR and SDS-PAGE. The Tras-NP exhibited a sustained, pH-sensitive drug release, with significantly enhanced release at acidic pH (85% at pH 5.0 vs. 65% at pH 7.4), ideal for intracellular delivery after endocytosis. In vitro cytotoxicity assays demonstrated the system's specificity and efficacy. Against HER2-overexpressing SK-BR-3 cells, Tras-NP showed superior cytotoxicity compared to non-targeted nanoparticles and free docetaxel. This enhanced effect was absent in HER2-negative MCF-7 cells, confirming HER2-dependent targeting. The Tras-NP platform successfully combines active targeting with controlled release, representing a promising strategy to enhance therapeutic efficacy and reduce off-target effects in HER2-positive breast cancer.
