Eradication of CD44-variant positive population in head and neck tumors through controlled intracellular navigation of cisplatin-loaded nanomedicines

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• 作者：Ming Wang^a ; ¹ ; Yutaka Miura^b ; ¹ ; Kenji Tsuchihashi^c ; ^d ; Kazuki Miyano^b ; Osamu Nagano^c ; Momoko Yoshikawa^c ; Ami Tanabe^b ; Jun Makino^b ; Yuki Mochida^e ; Nobuhiro Nishiyama^e ; ^f ; Hideyuki Saya^c ; Horacio Cabral^g ; ^{horacio@bmw.t.u-tokyo.ac.jp" class="auth_mail" title="E-mail the corresponding author} ; Kazunori Kataoka^a ; ^b ; ^e ; ^g ; ^h ; ^{kataoka@bmw.t.u-tokyo.ac.jp" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Drug delivery ; Polymeric micelle ; CD44-variant ; Head and neck tumor ; Cancer therapy
• 刊名：Journal of Controlled Release
• 出版年：2016
• 出版时间：28 May 2016
• 年：2016
• 卷：230
• 期：Complete
• 页码：26-33
• 全文大小：1201 K

文摘

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.