RRC ID 52277
Author Miyano K, Cabral H, Miura Y, Matsumoto Y, Mochida Y, Kinoh H, Iwata C, Nagano O, Saya H, Nishiyama N, Kataoka K, Yamasoba T.
Title cRGD peptide installation on cisplatin-loaded nanomedicines enhances efficacy against locally advanced head and neck squamous cell carcinoma bearing cancer stem-like cells.
Journal J Control Release
Abstract Recalcitrant head and neck squamous cell carcinoma (HNSCC) usually relapses after therapy due to the enrichment of drug resistant cancer stem-like cells (CSCs). Nanomedicines have shown potential for eradicating both cancer cells and CSCs by effective intratumoral navigation for reaching particular cell populations and controlling drug delivery. The installation of ligands on nanomedicines is an attractive approach for improving the delivery to CSCs within tumors, though the development of CSC-selective ligand-receptor systems has been challenging. Herein, we found that the CSC subpopulation in HNSCC cells overexpresses αvβ5 integrins, which is preferentially expressed in tumor neovasculature and cancer cells, and can be effectively targeted by using cyclic Arg-Gly-Asp (cRGD) peptide. Thus, in this study, we propose installing cRGD peptide on micellar nanomedicines incorporating cisplatin for improving their activity against CSCs and enhancing survival. Both cisplatin-loaded micelles (CDDP/m) and cRGD-installed CDDP/m (cRGD-CDDP/m) were effective against HNSCC SAS-L1-Luc cells in vitro, though cRGD-installed CDDP/m was more potent than CDDP/m against the CSC fraction. In vivo, the cRGD-CDDP/m also showed significant antitumor activity against HNSCC orthotopic tumors, i.e. SAS-L1 and HSC-2. Moreover, cRGD-CDDP/m rapidly accumulated into the lymph node metastasis of SAS-L1 tumors, effectively inhibiting their growth, and prolonging mice survival. These findings indicate cRGD-installed nanomedicines as an advantageous strategy for targeting CSCs in HNSCC, and particularly, cRGD-CDDP/m as a significant therapeutic strategy against regionally advanced HNSCC.
Volume 261
Pages 275-286
Published 2017-9-10
DOI 10.1016/j.jconrel.2017.06.021
PII S0168-3659(17)30685-5
PMID 28666729
MeSH Animals Antineoplastic Agents / administration & dosage* Antineoplastic Agents / pharmacology Carcinoma, Squamous Cell / drug therapy* Carcinoma, Squamous Cell / pathology Cell Line, Tumor Cisplatin / administration & dosage* Cisplatin / pharmacology Drug Carriers / chemistry Drug Delivery Systems Female Head and Neck Neoplasms / drug therapy* Head and Neck Neoplasms / pathology Humans Lymphatic Metastasis Mice Mice, Inbred BALB C Mice, Nude Micelles Nanoparticles Neoplastic Stem Cells / metabolism Peptides, Cyclic / chemistry* Squamous Cell Carcinoma of Head and Neck
IF 7.877
Human and Animal Cells HSC-2(RCB1945)