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

• Published in: International journal of nanomedicine 2019-09, Vol.14, p.7549-7560
• Main Authors: Su, Zhan, Liu, Duanqin, Chen, Liying, Zhang, Jun, Ru, Lu, Chen, Zhiyu, Gao, Zhennan, Wang, Xuxia
• Format: Article
• Language: English
• Subjects: Alternating magnetic field; Animals; Antibodies; Apoptosis; Cancer; Cancer metastasis; Cancer research; Cancer stem cells; Cancer treatment; Carcinoma; Cell Line, Tumor; Cell membranes; Cell Proliferation; Chemotherapy; EDTA; Endocytosis; Ferric oxide; Gene Expression Regulation, Neoplastic; Humans; Hyaluronan Receptors - metabolism; Iron compounds; Magnetic Fields; Magnetic nanoparticles; Magnetite Nanoparticles - therapeutic use; Magnetite Nanoparticles - ultrastructure; Male; Mice, Inbred BALB C; Mice, Nude; Microscopy; Nanoparticles; Neoplastic Stem Cells - pathology; Original Research; Polymerase chain reaction; Radiotherapy; Recurrence (Disease); Squamous cell carcinoma; Squamous Cell Carcinoma of Head and Neck - genetics; Squamous Cell Carcinoma of Head and Neck - pathology; Squamous Cell Carcinoma of Head and Neck - therapy; Stem cell transplantation; Stem cells; Tumor targeting; Tumors
• ISSN: 1178-2013; 1176-9114; 1178-2013
• DOI: 10.2147/IJN.S215087

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. 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. 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. 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.