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

Ming Wang, Yutaka Miura, Kenji Tsuchihashi, Kazuki Miyano, Osamu Nagano, Momoko Yoshikawa, Ami Tanabe, Jun Makino, Yuki Mochida, Nobuhiro Nishiyama, Hideyuki Saya, Horacio Cabral, Kazunori Kataoka

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)26-33
Number of pages8
JournalJournal of Controlled Release
Volume230
DOIs
Publication statusPublished - 2016 May 28

Fingerprint

Nanomedicine
Cisplatin
Neck
Head
Neoplastic Stem Cells
Population
Neoplasms
Platinum
Growth
Stem Cell Niche
Recurrence
Micelles
Therapeutics
Head and Neck Neoplasms
Glutathione
Polymers
Immunohistochemistry
Drug Therapy
DNA

Keywords

  • Cancer therapy
  • CD44-variant
  • Drug delivery
  • Head and neck tumor
  • Polymeric micelle

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Eradication of CD44-variant positive population in head and neck tumors through controlled intracellular navigation of cisplatin-loaded nanomedicines. / Wang, Ming; Miura, Yutaka; Tsuchihashi, Kenji; Miyano, Kazuki; Nagano, Osamu; Yoshikawa, Momoko; Tanabe, Ami; Makino, Jun; Mochida, Yuki; Nishiyama, Nobuhiro; Saya, Hideyuki; Cabral, Horacio; Kataoka, Kazunori.

In: Journal of Controlled Release, Vol. 230, 28.05.2016, p. 26-33.

Research output: Contribution to journalArticle

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 2016, 'Eradication of CD44-variant positive population in head and neck tumors through controlled intracellular navigation of cisplatin-loaded nanomedicines', Journal of Controlled Release, vol. 230, pp. 26-33. https://doi.org/10.1016/j.jconrel.2016.03.038
Wang, Ming ; Miura, Yutaka ; Tsuchihashi, Kenji ; Miyano, Kazuki ; Nagano, Osamu ; Yoshikawa, Momoko ; Tanabe, Ami ; Makino, Jun ; Mochida, Yuki ; Nishiyama, Nobuhiro ; Saya, Hideyuki ; Cabral, Horacio ; Kataoka, Kazunori. / Eradication of CD44-variant positive population in head and neck tumors through controlled intracellular navigation of cisplatin-loaded nanomedicines. In: Journal of Controlled Release. 2016 ; Vol. 230. pp. 26-33.
@article{ebde9ea5356146e885ceb6ee2fb0b1ee,
title = "Eradication of CD44-variant positive population in head and neck tumors through controlled intracellular navigation of cisplatin-loaded nanomedicines",
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.",
keywords = "Cancer therapy, CD44-variant, Drug delivery, Head and neck tumor, Polymeric micelle",
author = "Ming Wang and Yutaka Miura and Kenji Tsuchihashi and Kazuki Miyano and Osamu Nagano and Momoko Yoshikawa and Ami Tanabe and Jun Makino and Yuki Mochida and Nobuhiro Nishiyama and Hideyuki Saya and Horacio Cabral and Kazunori Kataoka",
year = "2016",
month = "5",
day = "28",
doi = "10.1016/j.jconrel.2016.03.038",
language = "English",
volume = "230",
pages = "26--33",
journal = "Journal of Controlled Release",
issn = "0168-3659",
publisher = "Elsevier",

}

TY - JOUR

T1 - Eradication of CD44-variant positive population in head and neck tumors through controlled intracellular navigation of cisplatin-loaded nanomedicines

AU - Wang, Ming

AU - Miura, Yutaka

AU - Tsuchihashi, Kenji

AU - Miyano, Kazuki

AU - Nagano, Osamu

AU - Yoshikawa, Momoko

AU - Tanabe, Ami

AU - Makino, Jun

AU - Mochida, Yuki

AU - Nishiyama, Nobuhiro

AU - Saya, Hideyuki

AU - Cabral, Horacio

AU - Kataoka, Kazunori

PY - 2016/5/28

Y1 - 2016/5/28

N2 - 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.

AB - 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.

KW - Cancer therapy

KW - CD44-variant

KW - Drug delivery

KW - Head and neck tumor

KW - Polymeric micelle

UR - http://www.scopus.com/inward/record.url?scp=84962636017&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84962636017&partnerID=8YFLogxK

U2 - 10.1016/j.jconrel.2016.03.038

DO - 10.1016/j.jconrel.2016.03.038

M3 - Article

C2 - 27040816

AN - SCOPUS:84962636017

VL - 230

SP - 26

EP - 33

JO - Journal of Controlled Release

JF - Journal of Controlled Release

SN - 0168-3659

ER -