The ultrasound wave enhanced carbon nanotube encapsulated dacarbazine effect on melanoma cell death via ER stress-mediated apoptosis

Abstract

BACKGROUND: In this study regarding the unique properties of carbon nanotubes (CNTs) to improve drug solubility, stability, and cellular uptake, combined with the mechanical effects of ultrasound wave, we aimed to elucidate how this synergistic approach influences cell death through endoplasmic reticulum stress (ER stress)-mediated apoptosis. By enhancing the bioavailability and effectiveness of DTIC through fSWCNTs and US, apoptosis rates can substantially increase, leading to improved therapeutic outcomes. MATERIALS AND METHOD: The dacarbazine (DTIC) was encapsulated in functionalized single-walled carbon nanotubes (fSWCNTs), and characterization of the synthesized fSWCNT-DTIC was evaluated using microscopic and spectrophotometric analysis. Then, the releasing rate of DTIC from fSWCNT was evaluated. Finally, the ER stress markers, cytotoxicity, apoptosis and necrosis rates, and cellular uptake were evaluated in the presence and absence of ultrasound wave in B16F10 cells by RT-PCR, MTT, and flow cytometry assays. RESULT: DTIC was encapsulated into SWCNTs with efficiency of 93.7, and the result confirmed by TEM analysis, FTIR spectrums, and zeta potential results. The release of the fSWCNT-DTIC in an acidic environment was more efficient compare with normal environment (61.59 Vs. 38.19). The application of ultrasound wave in the presence of fSWCNT-DTIC causes a significant increase in the GRP78 and IRE-1a levels, ROS production, apoptosis, and necrosis rate compared with control group (P < 0.05) in B16F10 cells. CONCLUSION: The induction of ER stress through fSWCNT- DTIC in conjunction with ultrasound waves is an innovative approach not only maximizes the cytotoxic effects of chemotherapy but also explores the vulnerability of tumor cells. Further elucidation of these mechanisms would enhance the clinical application of ultrasound in oncology.