Synergistic Action of Benzyl Isothiocyanate and Sorafenib in a Nanoparticle Delivery System for Enhanced Triple-Negative Breast Cancer Treatment.

ABSTRACT

Triple-negative breast cancer (TNBC) presents a therapeutic challenge due to its complex pathology and limited treatment options. Addressing this challenge, our study focuses on the effectiveness of combination therapy, which has recently become a critical strategy in cancer treatment, improving therapeutic outcomes and combating drug resistance and metastasis. We explored a novel combination therapy employing Benzyl isothiocyanate (BITC) and Sorafenib (SOR) and their nanoformulation, aiming to enhance therapeutic outcomes against TNBC. Through a series of in vitro assays, we assessed the cytotoxic effects of BITC and SOR, both free and encapsulated. The BITC-SOR-loaded nanoparticles (NPs) were synthesized using an amphiphilic copolymer, which demonstrated a uniform spherical morphology and favorable size distribution. The encapsulation efficiencies, as well as the sustained release profiles at varied pH levels, were quantified, revealing distinct kinetics that were well-modeled by the Korsmeyer-Peppas equation. The NP delivery system showed a marked dose-dependent cytotoxicity towards TNBC cells, with an IC50 of 7.8 µM for MDA-MB-231 cells, indicating improved efficacy over free drugs, while exhibiting minimal toxicity toward normal breast cells. Furthermore, the NPs significantly inhibited cell migration and invasion in TNBC models, surpassing the effects of free drugs. These findings underscore the potential of BITC-SOR-NPs as a promising therapeutic approach for TNBC, offering targeted delivery while minimizing systemic toxicity.