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

    25 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

    Bibliographical note

    Funding Information:
    This work was supported by the National Research Foundation of Korea (NRF) grants funded by the Korean Government (MEST) (20110027932 and 2012028831) and National R&D Program for Cancer Control, Ministry of Health and Welfare, Republic of Korea (1420390).

    Publisher Copyright:
    © 2017 Elsevier B.V.

    Keywords

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

    ASJC Scopus subject areas

    • Pharmaceutical Science

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