CD44-Targeted Magnetic Nanoparticles Kill Head And Neck Squamous Cell Carcinoma Stem Cells In An Alternating Magnetic Field

Abstract

Zhan Su,1,2 Duanqin Liu,1,2 Liying Chen,2 Jun Zhang,1,2 Lu Ru,2 Zhiyu Chen,2 Zhennan Gao,1,2,* Xuxia Wang1,2,* 1Shandong Provincial Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan, Shandong 250012, People’s Republic of China; 2Department of Oral and Maxillofacial Surgery, School of Stomatology, Shandong University, Jinan, Shandong 250012, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhennan Gao;Xuxia WangDepartment of Oral and Maxillofacial Surgery, School of Stomatology, Shandong University, 44-1 West Wenhua Road, Jinan, Shandong 250012, People’s Republic of ChinaTel +86 531 15169070891; +86 531 13906410670Email [email protected]; [email protected]: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignant tumor in the world. Studies in recent years have demonstrated that cancer stem cells (CSCs) are present in many tumor tissues, including HNSCC, and CSCs are the root cause of tumor recurrence and metastasis. Thus, taking new treatment measures to target the killing of CSCs that are resistant to chemotherapy and radiotherapy is key to the success of cancer treatment.Methods: We explored a method for preparing anti-CD44 antibody-modified superparamagnetic iron oxide nanoparticles (SPIONPs). Biocompatibility was evaluated by a CCK-8 assay. The CSCs were obtained by a 3D cell culture technique from Cal-27 (human oral squamous cell carcinoma) cells, and then the CSCs were identified by quantitative real-time polymerase chain reaction (qRT-PCR). The targeting efficiency of the CD44-SPIONPs to CSCs was confirmed by Prussian blue staining and visualized by laser scanning confocal microscopy (LSCM). Flow cytometry was used to detect the apoptosis of CSCs after alternating magnetic field (AMF) treatment. The efficacy of tumor growth inhibition by CD44-SPIONP-mediated magnetic hyperthermia therapy was evaluated with tumor xenografts in nude mice.Results: The CD44-SPIONPs exhibited no negative effect on CSCs, indicating good biocompatibility. After SPIONPs were cocultured with stem cells, the majority of CD44-SPIONPs labeled with FITC penetrated the cell membrane into the cytoplasm. After AMF treatment, CD44-SPIONPs induced CSCs to undergo programmed death. The inhibitory ratio of the treated group was 33.43%, and necrotic areas in the tumor tissue were mainly distributed around the magnetic fluid.Conclusion: These results demonstrate that it is possible to kill CSCs using targeted magnetic nanoparticles and an AMF and that magnetic fluid hyperthermia significantly inhibited the growth of grafted Cal-27 tumors in mice.Keywords: magnetic nanoparticles, cancer stem cells, alternating magnetic field, tumor targeting

Keywords

• Magnetic nanoparticles
• Cancer stem cells
• Alternating magnetic field
• Tumor targeting