Abstract

Simple SummaryTriple-negative breast cancer (TNBC) with negative expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 (HER2) is considered to be associated with poorer outcomes and a higher risk of recurrence or metastasis owing to a lack of effective targeted therapeutic drugs. The epidermal growth factor receptor (EGFR) functions is a driver of disease progression in most of TNBC that represents a viable target that can be leveraged to guide the intra-tumoral delivery of chemotherapeutic drugs in TNBC patients. Moreover, ultrasound-mediated cavitation (UMC) strategies increase tissue permeability and extravasation through nuclei-dependent cavitation via sonoporation, thus enabling drugs to better enter target tissues. In this research, a combination of active, targeting nano-micelles and UMC was able to inhibit TNBC tumor growth effectively at lower concentrations while reducing treatment-related toxicity. Thus, this is a very promising treatment strategy in the clinical therapy with TNBC and other cancer types.AbstractTriple-negative breast cancer (TNBC) is highly recurring and metastatic breast cancer with overexpressing epidermal growth factor receptor (EGFR). Herein, a series of in vitro and in vivo analyses were used to explore the therapeutic effect of EGFR-targeting nano-micelles (PLGA-PEG/[email protected]) combined with ultrasound-mediated cavitation (UMC). The prepared nano-micelle drug carriers have good biocompatibility and can greatly increase the drug accumulation in tumor regions, thereby reducing off-target toxicity while enhancing anti-tumor efficacy. Moreover, an in vivo analysis of the practical utility of this treatment modality was conducted by using SonoVueTMmicrobubbles to achieve cavitation under different power intensity levels, with an ultrasonic power intensity of 0.5 W/cm2maximizing the intra-tumoral blood perfusion. Relative to[email protected]/anti-EGFR nano-micelles treatment alone, t