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 language | English |
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Pages (from-to) | 258-269 |
Number of pages | 12 |
Journal | Journal of Controlled Release |
Volume | 255 |
DOIs | |
Publication status | Published - 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