RRC ID 51689
Author Wang M, Miura Y, Tsuchihashi K, Miyano K, Nagano O, Yoshikawa M, Tanabe A, Makino J, Mochida Y, Nishiyama N, Saya H, Cabral H, Kataoka K.
Title Eradication of CD44-variant positive population in head and neck tumors through controlled intracellular navigation of cisplatin-loaded nanomedicines.
Journal J Control Release
Abstract Eventual relapse of tumor growth is commonly observed in head and neck cancer patients, following treatment with platinum-based chemotherapies. This occurrence is believed to be related to the failure to eradicate drug resistant, cancer stem cell (CSC) niches, thereby enriching their population in tumors after treatment. In this study, we show that in contrast to free cisplatin (CDDP), the polymer micelle-based nanomedicine incorporating cisplatin (CDDP/m), can eradicate both the undifferentiated cell and the differentiated cancer cell populations within a head and neck tumor model. Immunohistochemistry of treated tumors showed that opposing to CDDP treatment, CDDP/m could reduce tumor growth without concentrating the CSC-like population. We further showed that CDDP/m, but not CDDP, can localize into hypoxic regions, possibly CSC-rich areas, in the tumors, and can overcome their detoxification mechanism based-on high cellular expression of glutathione to successfully deliver Pt to nuclear DNA. Our data suggests CDDP/m to be a replacement for current platinum therapies, for its ability to eradicate both bulk and CSC-like populations, and in turn to prevent recurrence of tumor growth.
Volume 230
Pages 26-33
Published 2016-5-28
DOI 10.1016/j.jconrel.2016.03.038
PII S0168-3659(16)30184-5
PMID 27040816
MeSH Aldehyde Dehydrogenase / metabolism Animals Antineoplastic Agents / administration & dosage* Antineoplastic Agents / pharmacology Antineoplastic Agents / therapeutic use Cell Line, Tumor Cell Survival / drug effects Cisplatin / administration & dosage* Cisplatin / pharmacology Cisplatin / therapeutic use DNA / metabolism Drug Carriers / administration & dosage* Drug Carriers / pharmacology Drug Carriers / therapeutic use Female Head and Neck Neoplasms / drug therapy* Head and Neck Neoplasms / metabolism Humans Hyaluronan Receptors / metabolism* Mice, Inbred BALB C Micelles Nanomedicine Platinum / metabolism
IF 7.727
Times Cited 9
Human and Animal Cells HSC-2(RCB1945)