Combining ultrasound technology with targeted fucoidan/arginine-gelatin nanoparticles loaded with doxorubicin to enhance therapeutic efficacy and modulate bioeffects in drug-resistant triple-negative breast cancer.

Triple-negative breast cancer (TNBC) presents formidable challenges due to its aggressive nature and high recurrence rates, compounded by the involvement of epithelial-mesenchymal transition (EMT) in its progression and metastasis. Standard chemotherapy, which typically employs doxorubicin (DOX), remains a primary treatment approach. However, multidrug resistance (MDR) mechanisms, which include ATP-binding cassette transporters and EMT, contribute to treatment failures. Ultrasound has emerged as a promising modality among the various strategies explored to address MDR in TNBC. It serves as a diagnostic tool and holds therapeutic potential by inducing various biological effects depending on the exposure level. Targeted nanoparticles offer a means to enhance drug delivery efficiency. Our study aims to advance ultrasound technology combined with biocompatible nanoparticles using simplified preparation methods to improve treatment outcomes for drug-resistant TNBC. In particular, employing DOX-loaded fucoidan/arginine-gelatin nanoparticles facilitated the targeted delivery of chemotherapy drugs to tumors by effectively interacting with P-selectin, resulting in tumor growth inhibition. Furthermore, these nanoparticles mitigated MDR and EMT, particularly when combined with ultrasound treatment. This integrated approach of nanoparticle delivery with ultrasonography opens up a promising and innovative avenue for clinical cancer research.