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 journalArticle

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.

Original languageEnglish
Pages (from-to)3107-3118
Number of pages12
JournalBioconjugate Chemistry
Volume30
Issue number12
DOIs
Publication statusPublished - 2019 Dec 18

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Tumors
Albumins
Molecules
Bearings (structural)
Neoplasms
Dyes
Fluorescence
Infrared radiation
Palmitic acid
Pharmacokinetics
Oncology
Surface plasmon resonance
CY5.5 cyanine dye
Electrophoresis
Fatty acids
Prodrugs
Peptides
Assays
Gels
Coloring Agents

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biomedical Engineering
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry

Cite this

A Comparative Study on Albumin-Binding Molecules for Targeted Tumor Delivery through Covalent and Noncovalent Approach. / Um, Wooram; Park, Jooho; Youn, Ahye; Cho, Hanhee; Lim, Seungho; Lee, Jong Won; Yoon, Hong Yeol; Lim, Dong Kwon; Park, Jae Hyung; Kim, Kwangmeyung.

In: Bioconjugate Chemistry, Vol. 30, No. 12, 18.12.2019, p. 3107-3118.

Research output: Contribution to journalArticle

Um, Wooram ; Park, Jooho ; Youn, Ahye ; Cho, Hanhee ; Lim, Seungho ; Lee, Jong Won ; Yoon, Hong Yeol ; Lim, Dong Kwon ; Park, Jae Hyung ; Kim, Kwangmeyung. / A Comparative Study on Albumin-Binding Molecules for Targeted Tumor Delivery through Covalent and Noncovalent Approach. In: Bioconjugate Chemistry. 2019 ; Vol. 30, No. 12. pp. 3107-3118.
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