Ultrasound-mediated paclitaxel-loaded EGFR nanoparticles for targeted therapy in breast cancer

Abstract

Paclitaxel (PTX)-loaded nanoparticles based on poly(lactic-co-glycolic acid) (PLGA) represent a promising platform for improving chemotherapeutic efficacy in triple-negative breast cancer (TNBC), a highly aggressive subtype with limited therapeutic targets and poor clinical outcomes. To address challenges of nonspecific distribution and systemic toxicity associated with conventional PTX treatment, we designed a multifunctional nanocarrier system integrating active targeting and ultrasound responsiveness. The nanoparticles (PTX@TNPs) were prepared using a double emulsion method, encapsulating PTX and perfluoropentane (PFP) in a PLGA matrix, followed by surface conjugation of GE11 peptides targeting the epidermal growth factor receptor (EGFR) via EDC/NHS chemistry. Comprehensive physicochemical characterization revealed favorable particle size, colloidal stability, and drug loading efficiency. In vitro studies using EGFR-overexpressing MDA-MB-231 cells demonstrated significantly enhanced cellular uptake and cytotoxicity of PTX@TNPs, especially under ultrasound irradiation. In vivo, PTX@TNPs combined with ultrasound markedly inhibited tumor growth, suppressed microvessel density, and induced apoptosis in a TNBC xenograft model, while exhibiting reduced systemic toxicity compared to free PTX. Histological and immunohistochemical staining confirmed downregulation of proliferation marker Ki-67 and angiogenesis marker CD31 in tumor tissues following treatment. These findings highlight the synergistic therapeutic potential of combining EGFR-mediated active targeting with ultrasound-triggered drug release and underscore the translational value of PTX@TNPs as a safe and efficient nanoplatform for TNBC treatment.