Theranostic iRGD peptide containing cisplatin prodrug: Dual-cargo tumor penetration for improved imaging and therapy

Hong Jun Cho, Sung Jun Park, Yoon Sik Lee, Sehoon Kim

Research output: Contribution to journalArticlepeer-review

30 Citations (Scopus)


In theranostics, peptide-based platforms have widely been exploited owing to their unique biological functions and chemical versatilities. As a tumor-homing ligand, internalizing RGD peptide (iRGD), composed of a tumor-targeting sequence (RGD) and a cell-penetrating C-end Rule (CendR) motif, is known to facilitate the tumor-specific delivery of payloads that are covalently conjugated on its N-terminal fragment or co-administered without any covalent linkages. However, theranostic uses of the iRGD-based platform remain in its infancy with its full potential unexplored; for instance, detailed mechanism of iRGD fragmentation during internalization, strategies for the tumor-specific release of payloads from iRGD and the role of the C-terminal iRGD fragment in delivery have yet to be revealed. In this study, we designed a dual-channel fluorescent cyclic iRGD (TAMRA-iRGDC-Cy5.5) to track each of the N- and C-terminal fragments separately during the tumor internalization process. It turned out that both fragments undergo translocation into cancer cells together and are localized within endosomal-lysosomal compartments. The resulting co-internalization of both iRGD fragments allowed us to develop a new theranostic peptide platform (Cy5.5-iRGDC-Pt(IV)) by conjugating a fluorescent dye and a cisplatin prodrug on each terminus of cyclic iRGD for simultaneous cancer-targeted imaging and therapy. Compared to a control peptide having a non-iRGD sequence, the Cy5.5-iRGDC-Pt(IV) did not only provide a better tumor imaging contrast but also induced tumor-specific apoptosis leading to efficacious tumor suppression. Besides the outstanding cancer imaging and therapeutic performance, the Cy5.5-iRGDC-Pt(IV) revealed negligible systemic toxicity, holding potential to be applied for theranostic uses.

Original languageEnglish
Pages (from-to)73-80
Number of pages8
JournalJournal of Controlled Release
Publication statusPublished - 2019 Apr 28

Bibliographical note

Funding Information:
This work was supported by grants from the National Research Foundation of Korea ( 2017M3A9D8029942 , and 2014M3C1A3054141 ), the Korea Health Industry Development Institute ( HI15C1540 ), the Development of Platform Technology for Innovative Medical Measurements Program from Korea Research Institute of Standards and Science ( KRISS-2018-GP2018-0018 ), and the Intramural Research Program of KIST.

Publisher Copyright:
© 2019 Elsevier B.V.

Copyright 2019 Elsevier B.V., All rights reserved.


  • Cancer imaging and therapy
  • CendR pathway
  • Cisplatin prodrug
  • Internalizing iRGD
  • Theranostic peptide

ASJC Scopus subject areas

  • Pharmaceutical Science


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