KIST / 조홍준, 김세훈*
Abstract
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.
Author information
Cho HJ1, Park SJ2, Lee YS3, Kim S4.
1
Center for Theragnosis, Korea Institute of Science and Technology, 5 Hwarang-ro 14-gil, Seongbuk-gu, Seoul 02792, Republic of Korea.
2
Center for Theragnosis, Korea Institute of Science and Technology, 5 Hwarang-ro 14-gil, Seongbuk-gu, Seoul 02792, Republic of Korea; School of Chemical and Biological Engineering, Seoul National University, Seoul 08826, Republic of Korea.
3
School of Chemical and Biological Engineering, Seoul National University, Seoul 08826, Republic of Korea.
4
Center for Theragnosis, Korea Institute of Science and Technology, 5 Hwarang-ro 14-gil, Seongbuk-gu, Seoul 02792, Republic of Korea; KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul 02841, Republic of Korea; Division of Bio-Medical Science & Technology, KIST School, Korea University of Science and Technology (UST), Seoul 02792, Republic of Korea. Electronic address: sehoonkim@kist.re.kr.
편집위원
이 논문에서 저자는 세포 투과를 가능하게 한 종양표적 RGD peptide (internalizing RGD, iRGD)에 이중 채널 광학영상이 가능하게끔 형광염료를 결합시킨 물질을 개발하였고, 이를 이용해 종양내 internalization 메커니즘 연구를 보여주었다. 이를 이용하여 종양의 진단 및 치료의 가능성을 제시하고 있다.
2019-05-28 18:00:19