KIST / 음우람, 박주호, 김광명*
Abstract
Various types of albumin-binding molecules have been conjugated to anticancer drugs, and these modified prodrugs could be effective in cancer treatments compared to free anticancer drugs. However, the tumor targeting of albumin-binding prodrugs has not been clearly investigated. Herein, we examined the in vitro and in vivo tumor-targeting efficiency of three different albumin-binding molecules including albumin-binding peptide (DICLPRWGCLW: PEP), fatty acid (palmitic acid: PA), and maleimide (MI), respectively. In order to characterize the different targeting efficiency of albumin-binding molecules, PEP, PA, or MI was chemically labeled with near-infrared fluorescence (NIRF) dye, Cy5.5, in resulting PEP-Cy5.5, PA-Cy5.5, and MI-Cy5.5. These NIRF dye-labeled albumin-binding molecules were physically or chemically bound to albumin via gentle incubation in aqueous conditions in vitro. Notably, PA-Cy5.5 with reversible and multivalent binding affinities formed stable albumin complexes, compared to PEP-Cy5.5 and MI-Cy5.5, confirmed via surface plasmon resonance measurement, gel electrophoresis assay, and albumin-bound column-binding test. In tumor-bearing mice model, the different albumin-binding affinities of PA-Cy5.5, PEP-Cy5.5, and MI-Cy5.5 greatly contributed to their tumor-targeting ability. Even though the binding affinity of PEP-Cy5.5 and MI-Cy5.5 to albumin is higher than that of PA-Cy5.5 in vitro, intravenous PA-Cy5.5 showed a higher tumor-targeting efficiency in tumor-bearing mice compared to that of PEP-Cy5.5 and MI-Cy5.5. The reversible and multivalent affinities of albumin-binding molecules to native serum albumin greatly increased the pharmacokinetics and tumor-targeting efficiency in vivo.
Author information
Um W1,2, Park J1, Youn A1, Cho H1, Lim S1, Lee JW3, Yoon HY1, Lim DK3, Park JH2,4, Kim K1,3.
1
Center for Theragnosis, Biomedical Research Institute , Korea Institute of Science and Technology , Seoul 02792 , Republic of Korea.
2
Department of Health Sciences and Technology, SAIHST , Sungkyunkwan University , Seoul 06351 , Republic of Korea.
3
KU-KIST Graduate School of Converging Science and Technology , Korea University , Seoul 02841 , Republic of Korea.
4
School of Chemical Engineering, College of Engineering , Sungkyunkwan University , Suwon 16419 , Republic of Korea.
편집위원
알부민을 기반으로 하는 항암제 연구는 여러 연구자에 의해 진행되어 왔지만, 알부민-prodrug의 암 표적 과정에 대한 정확한 연구는 많이 알려지진 않았다. 이 논문은 peptide (DICLPRWGCLW; PEP), fatty acid (plmitic acid; PA) 및 maleimide (MI)가 근적외선 형광염료 Cy5.5 표지된 알부민에 결합한 후 종양을 표적하는 효율을 측정한 평가 결과를 보여주고 있다.
2020-01-30 18:13:27