A Comparative Study on Albumin-Binding Molecules for Targeted Tumor Delivery through Covalent and Noncovalent Approach

Wooram Um, Jooho Park, Ahye Youn, Hanhee Cho, Seungho Lim, Jong Won Lee, Hong Yeol Yoon, Dong Kwon Lim, Jae Hyung Park, Kwangmeyung Kim

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


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.

Original languageEnglish
Pages (from-to)3107-3118
Number of pages12
JournalBioconjugate Chemistry
Issue number12
StatePublished - 18 Dec 2019

Bibliographical note

Funding Information:
This work was supported from the National Research Foundation (NRF) of South Korea, funded by the Ministry of Science (NRF-2019R1A2C3006283) of Republic of Korea, the KU-KIST Graduate School of Converging Science and Technology (Korea University), and the Intramural Research Program of KIST.

Publisher Copyright:
© 2019 American Chemical Society.


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