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Cited 18 time in webofscience Cited 18 time in scopus
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A Comparative Study on Albumin-Binding Molecules for Targeted Tumor Delivery through Covalent and Noncovalent Approach

Authors
Um, WooramPark, JoohoYoun, AhyeCho, HanheeLim, SeunghoLee, Jong WonYoon, Hong YeolLim, Dong-KwonPark, Jae HyungKim, Kwangmeyung
Issue Date
Dec-2019
Publisher
American Chemical Society
Citation
Bioconjugate Chemistry, v.30, no.12, pp 3107 - 3118
Pages
12
Indexed
SCI
SCIE
SCOPUS
Journal Title
Bioconjugate Chemistry
Volume
30
Number
12
Start Page
3107
End Page
3118
URI
https://scholarworks.korea.ac.kr/kumedicine/handle/2020.sw.kumedicine/28485
DOI
10.1021/acs.bioconjchem.9b00760
ISSN
1043-1802
1520-4812
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.
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