NDLI: A rapid albumin-binding 5-fluorouracil prodrug with a prolonged circulation time and enhanced antitumor activity

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Biomaterials Science Vol - 5 Issue - 2

Biomaterials Science Vol - 5 Issue - 1

Biomaterials Science Vol -4

Biomaterials Science Vol -3

Biomaterials Science Vol -2

Biomaterials Science Vol -1

A rapid albumin-binding 5-fluorouracil prodrug with a prolonged circulation time and enhanced antitumor activity

Content Provider	Royal Society of Chemistry (RSC)
Author	Zhao, Dongyang Sun, Jin Wei, Wei Zhang, Huicong He, Zhonggui Tao, Wenhui
Copyright Year	2017
Abstract	5-Fluorouracil (5-FU) is an antimetabolite widely used in the treatment of a variety of solid tumors. However, its clinical applications are greatly hindered by a very short residence time in blood circulation and non-specific distribution in the body. In order to overcome these challenges, 1-alkylcarbonyloxymethyl 5-FU was designed and linked with a maleimide group to form an albumin-binding 5-FU prodrug, named EMC-5-FU. In vitro incubation with bovine serum albumin (BSA) and fresh rat blood proved that the prodrug bound rapidly to cysteine-34 to form the drug–albumin conjugate nanomedicine. The conjugate BSA–EMC-5-FU was stable under acidic and neutral conditions but an unstable compound to release 5-FU in alkaline solution, and such a property was used for the determination of total 5-FU concentration in plasma. The t1/2 and AUC values of total 5-FU after an intravenous injection of EMC-5-FU to SD rats were significantly increased, about 43-fold and 93-fold higher than those of 5-FU following 5-FU intravenous administration, respectively. In vivo fluorescence images of EMC-Cy5 indirectly demonstrated the selective tumor accumulation of EMC-5-FU. In H22 tumor-bearing mice models, treatment with EMC-5-FU was more efficacious in tumor inhibition compared to 5-FU intravenous administration. In conclusion, a rapid albumin-binding prodrug strategy addresses concerns related to the poor circulation half-life and non-specific distribution of anticancer drugs, and paves the way for the development of in vivo-forming nanomedicines in clinical cancer therapy.
Starting Page	502
Ending Page	510
Page Count	9
File Format	HTM / HTML PDF
ISSN	20474830
Volume Number	5
Issue Number	3
Journal	Biomaterials Science
DOI	10.1039/c6bm00884d
Language	English
Publisher	Royal Society of Chemistry
Access Restriction	Open
Subject Keyword	Bovine serum albumin Maleimide Fluorescence Area under the curve (pharmacokinetics) Prodrug Dell EMC Blood plasma BSA Biological half-life Cysteine protease List of bus routes in London Nanomedicine Antimetabolite Fluorouracil Cancer
Content Type	Text
Resource Type	Article
Subject	Materials Science Biomedical Engineering

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Effect of Moderate UVC Irradiation on Bovine Serum Albumin and Complex with Antimetabolite 5-Fluorouracil: Fluorescence Spectroscopic and Molecular Modelling Studies

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Abbreviations: BSA- Bovine Serum Albumin

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A rapid albumin-binding 5-fluorouracil prodrug with a prolonged circulation time and enhanced antitumor activity

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