Assembly of polymer micelles through the sol-gel transition for effective cancer therapy

Nisar Ul Khaliq, Keun Sang Oh, Febrina Carolina Sandra, Yeonhee Joo, Juhyung Lee, Youngro Byun, In-San Kim, Ick Chan Kwon, Jae Hong Seo, Sang Yoon Kim, Soon Hong Yuk

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

Abstract

Photo-induced apoptosis-targeted chemotherapy (PIATC) was designed and characterized to propose a new protocol for improved chemotherapy. Intratumoral injection was selected as the mode of administration of the anticancer drug, doxorubicin (DOX). To extend the retention time of DOX at the tumor parenchyma, in-situ gel formation was induced through the sol-gel transition of the Pluronic NPs containing a prodrug of DOX or a photosensitizer. The prodrug (DEVD-S-DOX) was designed to be inactive with a peptide moiety (Aspartic acid-Glutamic acid-Valine-Aspartic acid: DEVD) linked to DOX and to be cleaved into free DOX by caspase-3 expressed with apoptosis. For reactive oxygen species (ROS)-mediated apoptosis, photo-irradiation with methylene blue (MB, photosensitizer) was utilized. The sol-gel transition of the Pluronic NPs containing reactive species, DEVD-S-DOX or MB, was examined by measuring the cloud point and the gel strength in response to temperature change. ROS-mediated apoptosis was observed by measuring the ROS and membrane integrity with induced apoptosis. The in vivo antitumor efficacy of PIATC was measured with a cardiotoxicity assay in tumor-bearing mice.

Original languageEnglish
Pages (from-to)258-269
Number of pages12
JournalJournal of Controlled Release
Volume255
DOIs
Publication statusPublished - 2017 Jun 10

Keywords

  • Apoptosis
  • Photodynamic therapy
  • Pluronic nanoparticles
  • Prodrug
  • Sol-gel transition

ASJC Scopus subject areas

  • Pharmaceutical Science

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