Modulation of the triggered apoptosis by nano emodin transfersome-mediated sonodynamic therapy on head and neck squamous cell carcinoma cell lines

Maryam Pourhajibagher; Shahroo Etemad-Moghadam; Mojgan Alaeddini; Abbas Bahador

doi:10.1016/j.pdpdt.2021.102253

Modulation of the triggered apoptosis by nano emodin transfersome-mediated sonodynamic therapy on head and neck squamous cell carcinoma cell lines

Photodiagnosis Photodyn Ther. 2021 Jun:34:102253. doi: 10.1016/j.pdpdt.2021.102253. Epub 2021 Mar 9.

Authors

Maryam Pourhajibagher¹, Shahroo Etemad-Moghadam¹, Mojgan Alaeddini¹, Abbas Bahador²

Affiliations

¹ Dental Research Center, Dentistry Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
² Oral Microbiology Laboratory, Department of Microbiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Fellowship in Clinical Laboratory Sciences, Iran University of Medical Sciences, Tehran, Iran. Electronic address: abahador@sian.tums.ac.ir.

PMID: 33711532
DOI: 10.1016/j.pdpdt.2021.102253

Abstract

Background: Non-invasive sonodynamic therapy (SDT) is a new treatment modality that uses low-intensity ultrasound to activate a non-toxic sensitizing chemical agent for cancer therapy in a site-directed manner. This study aimed to investigate the anti-cancer effects of ultrasound combined with nano emodin transfersome (NET) on head and neck squamous cell carcinoma (HNSCC) cell lines.

Materials and methods: A transfersome form of nano emodin as a novel sono-responsive nanomaterial was synthesized to enhance the accumulation and penetration of nanoparticles. iIn vitro experiments including hemolytic activity, cell proliferation, intracellular reactive oxygen species (ROS) generation, apoptosis induction, DNA fragmentation, and mRNA expressions of caspase 3 and 9 were conducted to explore the anti-cancer effects of NET-SDT on FaDu and CAL-27 cell lines.

Results: Characterization tests showed the round and uniform morphology of NET with transfersome structure, resulting in a high drug-loading content and encapsulation efﬁciency. No significant hemolytic activity was observed (P > 0.05). Cytotoxicity gradually increased with increasing concentrations of NET, so that 10 × 10^-4 g/L of NET plus 5 min ultrasound irradiation at a frequency of 1 MHz and ultrasonic intensity of 2 W/cm² effectively killed 98.2 % and 97.3 % of FaDu and CAL-27 cell lines, respectively (P < 0.05). We found that ROS generation in NET-SDT was dose-dependent and the triggered apoptosis and caspase-3/9 gene expression levels were significantly enhanced as the concentration of NET increased (P < 0.05). No significant difference was found in the rate of apoptosis induction and gene expression between two cell lines.

Conclusions: Our data demonstrated that SDT with NET as a sonosensitizer can induce apoptosis and significantly decrease cell viability of HNSCC cell lines, which represents the role of NET-SDT as a potent anti-cancer modality.

Keywords: Apoptosis; Caspase; Emodin; Gene expression; Oral cancer; Sonodynamic therapy.

MeSH terms

Apoptosis
Cell Line
Cell Line, Tumor
Emodin* / pharmacology
Head and Neck Neoplasms* / therapy
Humans
Photochemotherapy* / methods
Photosensitizing Agents / pharmacology
Reactive Oxygen Species
Squamous Cell Carcinoma of Head and Neck / drug therapy
Ultrasonic Therapy*

Substances

Photosensitizing Agents
Reactive Oxygen Species
Emodin