Anticancer therapeutic self-aggregates of sphingolipid metabolite-grafted poly(amino acid)-derivative and their enhanced intracellular delivery

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Novel sphingolipid metabolite conjugated poly(amino acid)-derivative, poly-alpha,beta-(2-hydroxylethyl L-aspartamide)-g-phytosphingosine copolymer, was designed as an anticancer prodrug-type carrier for enhanced intracellular uptake and physicochemical properties of polymeric micelle-like aggregates were evaluated. The resultant micelle-like aggregates showed a spherical shape and uniform size with a diameter less than 20 nm in an aqueous solution upon the increased number of phytosphingosine grafts. By the steady-state fluorescence of pyrene in aqueous polymer solutions, critical aggregation concentration (CAC) was obtained in the range of 0.166-0.0036 mg/ml and K(v), equilibrium partition constants of the pyrene in the self-aggregate solutions were estimated to be from 2.39 x 10(3) to 1.96 x 10(6). Phytosphingosine-grafted polymeric micelle-like aggregates as small as 20 nm were efficiently delivered into various cancer cell lines including oral, breast and colon carcinoma with the extent which is comparable to the level of targeting carrier system. The enhanced cellular uptake and anticancer therapeutic effect was evaluated by flow cytometry, confocal laser scanning microscopy (CLSM), and MIT assay. (C) 2010 The Korean Society of Industrial and Engineering Chemistry. Published by Elsevier B.V. All rights reserved.
Publisher
ELSEVIER SCIENCE INC
Issue Date
2010-11
Language
English
Article Type
Article
Keywords

MULTIFUNCTIONAL POLYMERIC MICELLES; APOPTOTIC CELL-DEATH; DRUG-DELIVERY; POLY(ASPARTIC ACID); CANCER-CELLS; PHYTOSPHINGOSINE; FLUORESCENCE; WATER; DERIVATIVES; BEHAVIOR

Citation

JOURNAL OF INDUSTRIAL AND ENGINEERING CHEMISTRY, v.16, no.6, pp.1011 - 1018

ISSN
1226-086X
DOI
10.1016/j.jiec.2010.09.008
URI
http://hdl.handle.net/10203/99216
Appears in Collection
CBE-Journal Papers(저널논문)
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