Self-targeted salinomycin-loaded DSPE-PEG-methotrexate nanomicelles for targeting both head and neck squamous cell carcinoma cancer cells and cancer stem cells

Minhui Zhu; Shicai Chen; Libo Hua; Caiyun Zhang; Mengjie Chen; Donghui Chen; Yinmei Dong; Yingying Zhang; Meng Li; Xianmin Song; Huaiwen Chen; Hongliang Zheng

doi:10.2217/nnm-2016-0382

Self-targeted salinomycin-loaded DSPE-PEG-methotrexate nanomicelles for targeting both head and neck squamous cell carcinoma cancer cells and cancer stem cells

Nanomedicine (Lond). 2017 Feb;12(4):295-315. doi: 10.2217/nnm-2016-0382. Epub 2017 Jan 17.

Authors

Minhui Zhu¹, Shicai Chen¹, Libo Hua¹, Caiyun Zhang¹, Mengjie Chen¹, Donghui Chen¹, Yinmei Dong¹, Yingying Zhang¹, Meng Li¹, Xianmin Song¹, Huaiwen Chen^{1

2}, Hongliang Zheng¹

Affiliations

¹ Department of Otolaryngology Head & Neck Surgery, Shanghai Changhai Hospital, the Second Military Medical University, 168 Changhai Road, Shanghai 200433, China.
² Sunlipo Biotech Research Center for Nanomedicine, 3688 Tingwei Road, Shanghai 201507, China.

PMID: 28093940
DOI: 10.2217/nnm-2016-0382

Abstract

Aim: To target both head and neck squamous cell carcinoma (HNSCC) cells and cancer stem cells (CSCs) by salinomycin-loaded DSPE-PEG-MTX (synthesized using DSPE-PEG2000-NH2 and methotrexate) nanomicelles (M-SAL-MTX).

Materials & methods: The characterization, antitumor activity and mechanism of M-SAL-MTX were evaluated.

Results & conclusion: M-SAL-MTX showed enhanced inhibitory effect toward both HNSCC CSCs and non-CSCs compared with a single treatment of methotrexate and salinomycin. In nude mice-bearing HNSCC xenografts, M-SAL-MTX suppressed tumor growth more effectively than other controls including combination of methotrexate and salinomycin. Therefore, M-SAL-MTX may provide a strategy for treating HNSCC by targeting both HNSCC CSCs and HNSCC cells.

Keywords: cancer stem cell; head and neck squamous cell carcinoma; methotrexate; nanomicelles; salinomycin.

MeSH terms

Animals
Anti-Bacterial Agents / administration & dosage*
Anti-Bacterial Agents / pharmacology
Anti-Bacterial Agents / therapeutic use
Antimetabolites, Antineoplastic / administration & dosage*
Antimetabolites, Antineoplastic / pharmacology
Antimetabolites, Antineoplastic / therapeutic use
Carcinoma, Squamous Cell / drug therapy*
Carcinoma, Squamous Cell / pathology
Cell Line, Tumor
Drug Carriers / chemistry*
Drug Delivery Systems
Head and Neck Neoplasms / drug therapy*
Head and Neck Neoplasms / pathology
Humans
Male
Methotrexate / administration & dosage*
Methotrexate / pharmacology
Methotrexate / therapeutic use
Mice, Inbred BALB C
Mice, Nude
Micelles
Neoplastic Stem Cells / drug effects*
Neoplastic Stem Cells / pathology
Phosphatidylethanolamines / chemistry
Polyethylene Glycols / chemistry
Pyrans / administration & dosage*
Pyrans / pharmacology
Pyrans / therapeutic use
Squamous Cell Carcinoma of Head and Neck

Substances

Anti-Bacterial Agents
Antimetabolites, Antineoplastic
Drug Carriers
Micelles
Phosphatidylethanolamines
Pyrans
1,2-distearoylphosphatidylethanolamine
Polyethylene Glycols
salinomycin
Methotrexate