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

Int J Biol Macromol. 2024 Dec;283(Pt 2):137764. doi: 10.1016/j.ijbiomac.2024.137764. Epub 2024 Nov 16.

Abstract

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.

Keywords: Fucoidan; Triple-negative breast cancer; Ultrasound.

MeSH terms

  • Animals
  • Arginine* / chemistry
  • Cell Line, Tumor
  • Doxorubicin* / chemistry
  • Doxorubicin* / pharmacology
  • Drug Carriers / chemistry
  • Drug Delivery Systems
  • Drug Resistance, Neoplasm* / drug effects
  • Epithelial-Mesenchymal Transition / drug effects
  • Female
  • Gelatin* / chemistry
  • Humans
  • Mice
  • Nanoparticles* / chemistry
  • P-Selectin / metabolism
  • Polysaccharides* / chemistry
  • Triple Negative Breast Neoplasms* / diagnostic imaging
  • Triple Negative Breast Neoplasms* / drug therapy
  • Triple Negative Breast Neoplasms* / pathology
  • Xenograft Model Antitumor Assays

Substances

  • Doxorubicin
  • Gelatin
  • fucoidan
  • Polysaccharides
  • Arginine
  • Drug Carriers
  • P-Selectin