One-pot synthesis of reactive oxygen species (ROS)-self-immolative polyoxalate prodrug nanoparticles for hormone dependent cancer therapy with minimized side effects

Anita Hocherl, Eliézer Jager, Alessandro Jager, Martin Hruby, Rafal Konefal, Olga Janouskova, Jiri Spevacek, Yaming Jiang, Peter W. Schmidt, Timothy P. Lodge, Petr Stepanek

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

A new reactive oxygen species (ROS)-sensitive, self-immolative biodegradable polyoxalate prodrug based on the anticancer chemotherapeutic hormone analog diethylstilbestrol was synthesized via one-pot step-growth polymerization. The nanoparticles prepared from this prodrug undergo self-immolative degradation releasing the chemotherapeutic drug in ROS-rich environments, e.g., in cancer cells. This new ROS self-immolative polyprodrug backbone eliminates the need for a linker between polymer chain and drug, resulting in a more specific drug release and minimized toxic side effects to non-ROS-producing cells as proven by in vitro experiments. The strategy enables re-utilization of a successful chemotherapeutic agent that has been clinically under-utilized due to dose-related side effects.

Original languageEnglish (US)
Pages (from-to)1999-2004
Number of pages6
JournalPolymer Chemistry
Volume8
Issue number13
DOIs
StatePublished - Apr 7 2017

Bibliographical note

Funding Information:
The financial support of the Ministry of Education, Youth and Sports (grants # LH14079, POLYMAT #LO1507), the Czech Science Foundation (grant # 16-02870S, 15-13853S and 17-09998S), and the National Science Foundation through the University of Minnesota MRSEC, Award DMR-1420013 is gratefully appreciated.

Publisher Copyright:
© 2017 The Royal Society of Chemistry.

How much support was provided by MRSEC?

  • Partial

Reporting period for MRSEC

  • Period 3

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