TY - JOUR T1 - Novel TSPO-targeted Doxorubicin Prodrug for Colorectal Carcinoma Cells JF - Anticancer Research JO - Anticancer Res SP - 5371 LP - 5378 DO - 10.21873/anticanres.14545 VL - 40 IS - 10 AU - JEMIANNE B. JIA AU - XIAOXI LING AU - MINZHI XING AU - JOHANNES M. LUDWIG AU - MINGFENG BAI AU - HYUN S. KIM Y1 - 2020/10/01 UR - http://ar.iiarjournals.org/content/40/10/5371.abstract N2 - Background/Aim: 18 kDa Translocator protein (TSPO) is a mitochondrial protein up-regulated in colorectal carcinoma (CRC). Our purpose was to develop a TSPO-targeted doxorubicin prodrug (Dox-TSPO) which can be loaded onto drug-eluting beads for transarterial chemoembolization. Furthermore, we evaluated its loading and release kinetics and effects on cell viability. Materials and Methods: N-Fmoc-DOX-14-O-hemiglutarate was coupled with a TSPO ligand, 6-TSPOmbb732, using classical N,N,N’,N’-tetramethyl-O-(1H-benzotriazol-1-yl)uranium hexafluorophosphate coupling to produce Dox-TSPO. Loading and elution studies were performed using DC beads™. Cell viability studies were performed using CellTiter-Glo® Luminescent Cell Viability Assay. Results: Dox-TSPO was successfully synthesized and readily loaded onto and eluted from DC beads™, albeit at a slower rate than free doxorubicin. CRC cell lines expressing TSPO were 2- to 4- fold more sensitive to Dox-TSPO compared to free doxorubicin at 72 h. Conclusion: Dox-TSPO is a promising candidate for targeted and directed cancer treatment of CRC liver metastases. ER -