喜树碱
化学
体内
癌症研究
癌细胞
前药
体外
药物输送
细胞内
结直肠癌
药理学
癌症
生物化学
生物
内科学
医学
有机化学
生物技术
作者
T. P. Singh,Tae Wan Kim,Akula S. N. Murthy,Mohuya Paul,Nasim Sepay,Hye Jeong Kong,Je‐Kyung Ryu,Nayeong Koo,Sohye Yoon,Keon-Hyoung Song,Moo Jun Baek,Seob Jeon,Jungkyun Im
标识
DOI:10.1016/j.ejmech.2023.116050
摘要
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.
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