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A Comparative Study on Albumin-Binding Molecules for Targeted Tumor Delivery through Covalent and Noncovalent Approach
journal contribution
posted on 2019-12-02, 22:30 authored by Wooram Um, Jooho Park, Ahye Youn, Hanhee Cho, Seungho Lim, Jong Won Lee, Hong Yeol Yoon, Dong-Kwon Lim, Jae Hyung Park, Kwangmeyung KimVarious 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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albumin-binding moleculesaffinityMI-Cy 5.5.DICLPRWGCLWTargeted Tumor DeliveryPA-Cy 5.5MI-Cy 5.5tumor-targeting efficiencyanticancer drugsalbumin-bound column-binding testtumor-bearing mice modelNIRF dye-labeled albumin-binding moleculesPEP-Cy 5.5vivo tumor-targeting efficiencygel electrophoresis assaysurface plasmon resonance measurement
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