The novel strategy for concurrent chemoradiotherapy by conjugating the apoptotic cell-binding moiety to caspase-3 activated doxorubicin prodrug

Young Seok Cho, Seung Woo Chung, Ha Rin Kim, Tae Hyung Won, Jeong Uk Choi, In-San Kim, Sang Yoon Kim, Youngro Byun

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

The selective targeting of cytotoxic agents to a tumor has shown limited success by difficulties in identifying the appropriate target molecules, and more importantly, by the phenotypically dynamic nature of the tumor cells and intratumoral heterogeneity. In an attempt to overcome these issues and efficiently deliver cytotoxic drugs to the tumor, we previously reported a strategy termed radiation-induced apoptosis-targeted chemotherapy (RIATC), which utilizes the radiotherapy for intentionally triggering the caspase-3 and in situ amplification of tumor apoptosis by caspase-3 activated prodrug. Herein, we propose an advanced form of RIATC prodrug, AP1-DEVD-S-DOX, that could more actively target to the ligands of radiation-induced tumor cells, which could accumulate more prodrugs, thereby allowing more effective in situ activation and amplification of tumor apoptosis, comparing to RIATC. Indeed, AP1-DEVD-S-DOX was able to exert improved doxorubicin (DOX) delivery to the tumor and anticancer effect than the RIATC prodrug that lacks apoptotic cell-binding property but having a similar degree of off-target distribution in the other organs. Accordingly, AP1-DEVD-S-DOX could be an efficient prodrug for concurrent chemoradiotherapy by selectively delivering doxorubicin to the tumor with less systemic cytotoxicity.

Original languageEnglish
Pages (from-to)241-249
Number of pages9
JournalJournal of Controlled Release
Volume296
DOIs
Publication statusPublished - 2019 Feb 28

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Prodrugs
Chemoradiotherapy
Caspase 3
Doxorubicin
Apoptosis
Neoplasms
Radiation
Drug Therapy
Radiation Effects
Cytotoxins
Radiotherapy
Ligands
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

The novel strategy for concurrent chemoradiotherapy by conjugating the apoptotic cell-binding moiety to caspase-3 activated doxorubicin prodrug. / Cho, Young Seok; Chung, Seung Woo; Kim, Ha Rin; Won, Tae Hyung; Choi, Jeong Uk; Kim, In-San; Kim, Sang Yoon; Byun, Youngro.

In: Journal of Controlled Release, Vol. 296, 28.02.2019, p. 241-249.

Research output: Contribution to journalArticle

Cho, Young Seok ; Chung, Seung Woo ; Kim, Ha Rin ; Won, Tae Hyung ; Choi, Jeong Uk ; Kim, In-San ; Kim, Sang Yoon ; Byun, Youngro. / The novel strategy for concurrent chemoradiotherapy by conjugating the apoptotic cell-binding moiety to caspase-3 activated doxorubicin prodrug. In: Journal of Controlled Release. 2019 ; Vol. 296. pp. 241-249.
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