Tumor-homing peptide iRGD-conjugate enhances tumor accumulation of camptothecin for colon cancer therapy
- Abstract
- Poor intracellular uptake of therapeutics in the tumor parenchyma is a key issue in cancer therapy. We describe a novel approach to enhance tumor targeting and achieve targeted delivery of camptothecin (CPT) based on a tumor-homing internalizing RGD peptide (iRGD). We synthesized an iRGD-camptothecin conjugate (iRGD-CPT) covalently coupled by a heterobifunctional linker and evaluated its in vitro and in vivo activity in human colon cancer cells. In vitro studies revealed that iRGD-CPT penetrated cells efficiently and reduced colon cancer cell viability to a significantly greater extent at micromolar concentrations than did the parent drug. Furthermore, iRGD-CPT showed high distribution toward tumor tissue, effectively suppressed tumor progression, and showed enhanced antitumor effects relative to the parent drug in a mouse model, demonstrating that iRGD-CPT is effective in vivo cancer treatment. These results suggest that intracellular delivery of CPT via the iRGD peptide is a promising drug delivery strategy that will facilitate the development of CPT derivatives and prodrugs with improved efficacy.
- All Author(s)
- Tejinder Singh
; Tae Wan Kim
; Akula S N Murthy
; Mohuya Paul
; Nasim Sepay
; Hye Jeong Kong
; Jae Sung Ryu
; Na Rim Koo
; Sujeong Yoon
; Keon-Hyoung Song
; Moo Jun Baek
; Seob Jeon
; Jungkyun Im
- Issued Date
- 2024
- Type
- Article
- Keyword
- Camptothecin; Colon cancer; Drug delivery; Tumor–homing and tumor-penetrating peptide; iRGD
- Publisher
- Elsevier
- ISSN
- 0223-5234
; 1768-3254
- Citation Title
- European journal of medicinal chemistry
- Citation Volume
- 265
- Citation Start Page
- 116050
- Language(ISO)
- eng
- DOI
- 10.1016/j.ejmech.2023.116050
- URI
- http://schca-ir.schmc.ac.kr/handle/2022.oak/1302
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