Skip to main content
  • AACR Journals
    • Blood Cancer Discovery
    • Cancer Discovery
    • Cancer Epidemiology, Biomarkers & Prevention
    • Cancer Immunology Research
    • Cancer Prevention Research
    • Cancer Research
    • Clinical Cancer Research
    • Molecular Cancer Research
    • Molecular Cancer Therapeutics

AACR logo

  • Register
  • Log in
  • My Cart
Advertisement

Main menu

  • Home
  • About
    • The Journal
    • AACR Journals
    • Subscriptions
    • Permissions and Reprints
    • Reviewing
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • Meeting Abstracts
    • Collections
      • COVID-19 & Cancer Resource Center
      • Focus on Radiation Oncology
      • Novel Combinations
      • Reviews
      • Editors' Picks
      • "Best of" Collection
  • For Authors
    • Information for Authors
    • Author Services
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • Editors' Picks
    • OnlineFirst
    • Citation
    • Author/Keyword
    • RSS Feeds
    • My Alert Summary & Preferences
  • News
    • Cancer Discovery News
  • COVID-19
  • Webinars
  • Search More

    Advanced Search

  • AACR Journals
    • Blood Cancer Discovery
    • Cancer Discovery
    • Cancer Epidemiology, Biomarkers & Prevention
    • Cancer Immunology Research
    • Cancer Prevention Research
    • Cancer Research
    • Clinical Cancer Research
    • Molecular Cancer Research
    • Molecular Cancer Therapeutics

User menu

  • Register
  • Log in
  • My Cart

Search

  • Advanced search
Molecular Cancer Therapeutics
Molecular Cancer Therapeutics
  • Home
  • About
    • The Journal
    • AACR Journals
    • Subscriptions
    • Permissions and Reprints
    • Reviewing
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • Meeting Abstracts
    • Collections
      • COVID-19 & Cancer Resource Center
      • Focus on Radiation Oncology
      • Novel Combinations
      • Reviews
      • Editors' Picks
      • "Best of" Collection
  • For Authors
    • Information for Authors
    • Author Services
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • Editors' Picks
    • OnlineFirst
    • Citation
    • Author/Keyword
    • RSS Feeds
    • My Alert Summary & Preferences
  • News
    • Cancer Discovery News
  • COVID-19
  • Webinars
  • Search More

    Advanced Search

Large Molecule Therapeutics

Preclinical Evaluation of a Cabazitaxel Prodrug Using Nanoparticle Delivery for the Treatment of Taxane-Resistant Malignancies

Binbin Xie, Jianqin Wan, Xiaona Chen, Weidong Han and Hangxiang Wang
Binbin Xie
1The First Affiliated Hospital, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, PR China.
2Department of Medical Oncology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, PR China.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Binbin Xie
Jianqin Wan
1The First Affiliated Hospital, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, PR China.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Xiaona Chen
1The First Affiliated Hospital, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, PR China.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Weidong Han
2Department of Medical Oncology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, PR China.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: wanghx@zju.edu.cn hanwd@zju.edu.cn
Hangxiang Wang
1The First Affiliated Hospital, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, PR China.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Hangxiang Wang
  • For correspondence: wanghx@zju.edu.cn hanwd@zju.edu.cn
DOI: 10.1158/1535-7163.MCT-19-0625 Published March 2020
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF
Loading

This article requires a subscription to view the full text. You may purchase access to this article or login to access your subscription using the links below.

Abstract

Taxane-based chemotherapeutics are clinically available as frontline treatment regimens for cervical cancer. However, drug resistance and life-threatening toxicity impair the clinical efficacy of taxanes, so more effective and less toxic therapeutic modalities are urgently needed. Cabazitaxel has attracted increasing interest due to its potential to circumvent the drug resistance by taxanes. We previously showed that tethering docosahexaenoic acid (DHA) to cabazitaxel enabled the prodrug to self-assemble into nanoparticles in water. Despite this encouraging finding, the DHA–cabazitaxel conjugate formulation requires further optimization to enhance nanoparticle retention and tumor delivery. We here integrated this conjugate into amphiphilic poly(ethylene glycol)-block-poly(D,L-lactic acid) copolymers to assemble dCTX NPs. The nanoparticle abrogated P-glycoprotein–mediated resistance in cancer cells. In a docetaxel-resistant cervical tumor xenograft-bearing mouse model, the efficacy was augmented by the nanotherapy when compared with solution-based free drugs (i.e., docetaxel and cabazitaxel). Dose intensification of dCTX NPs markedly suppressed the tumor growth in this model. Detailed studies revealed that systemic toxicity was alleviated, and MTD of dCTX NPs was at least 3 times higher than that of free cabazitaxel in animals, which may enable dose increases for clinical studies. In conclusion, the new formulation addresses essential requirements in terms of the stability, safety, and translational capacity for initiating early-phase clinical trials.

Footnotes

  • Note: Supplementary data for this article are available at Molecular Cancer Therapeutics Online (http://mct.aacrjournals.org/).

  • Mol Cancer Ther 2020;19:822–34

  • Received June 20, 2019.
  • Revision received November 7, 2019.
  • Accepted December 13, 2019.
  • Published first December 17, 2019.
  • ©2019 American Association for Cancer Research.
View Full Text

Log in using your username and password

Forgot your user name or password?

Purchase access

You may purchase access to this article. This will require you to create an account if you don't already have one.
PreviousNext
Back to top
Molecular Cancer Therapeutics: 19 (3)
March 2020
Volume 19, Issue 3
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Editorial Board (PDF)

Sign up for alerts

View this article with LENS

Open full page PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Molecular Cancer Therapeutics article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Preclinical Evaluation of a Cabazitaxel Prodrug Using Nanoparticle Delivery for the Treatment of Taxane-Resistant Malignancies
(Your Name) has forwarded a page to you from Molecular Cancer Therapeutics
(Your Name) thought you would be interested in this article in Molecular Cancer Therapeutics.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Preclinical Evaluation of a Cabazitaxel Prodrug Using Nanoparticle Delivery for the Treatment of Taxane-Resistant Malignancies
Binbin Xie, Jianqin Wan, Xiaona Chen, Weidong Han and Hangxiang Wang
Mol Cancer Ther March 1 2020 (19) (3) 822-834; DOI: 10.1158/1535-7163.MCT-19-0625

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Preclinical Evaluation of a Cabazitaxel Prodrug Using Nanoparticle Delivery for the Treatment of Taxane-Resistant Malignancies
Binbin Xie, Jianqin Wan, Xiaona Chen, Weidong Han and Hangxiang Wang
Mol Cancer Ther March 1 2020 (19) (3) 822-834; DOI: 10.1158/1535-7163.MCT-19-0625
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Introduction
    • Materials and Methods
    • Results
    • Discussion
    • Disclosure of Potential Conflicts of Interest
    • Authors' Contributions
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • PDF
Advertisement

Related Articles

Cited By...

More in this TOC Section

  • Novel Peptide Camptothecin Drug-Linkers for Potent ADCs
  • TriTAC Molecules Direct T Cells to Eliminate Solid Tumors
  • Potent TRAILR2-Mediated Tumor Cell Death via CDH17 Anchoring
Show more Large Molecule Therapeutics
  • Home
  • Alerts
  • Feedback
  • Privacy Policy
Facebook  Twitter  LinkedIn  YouTube  RSS

Articles

  • Online First
  • Current Issue
  • Past Issues
  • Meeting Abstracts

Info for

  • Authors
  • Subscribers
  • Advertisers
  • Librarians

About MCT

  • About the Journal
  • Editorial Board
  • Permissions
  • Submit a Manuscript
AACR logo

Copyright © 2021 by the American Association for Cancer Research.

Molecular Cancer Therapeutics
eISSN: 1538-8514
ISSN: 1535-7163

Advertisement