Oxidative stimuli-responsive nanoprodrug of camptothecin kills glioblastoma cells

Bioorganic & Medicinal Chemistry Letters
Bong-Seop LeeJohn S Yu

Abstract

The purpose of this study was to prepare and characterize nanometer-sized prodrug (nanoprodrug) of camptothecin. The camptothecin prodrug was synthesized using tetraethylene glycol spacer linked via carbonate bond to camptothecin and via ester bond to alpha-lipoic acid. The nanoprodrug was prepared through the spontaneous emulsification mechanism using the mixture of camptothecin prodrug and alpha-tocopherol which served as a structural matrix. The nanoprodrug was activated readily by porcine liver esterase and, with a much slower rate, by hydrolytic degradation. Upon longterm storage, the alpha-lipoic acid moiety of the camptothecin prodrug gradually oxidized without loss of structural integrity and therapeutic efficacy. Interestingly, the hydrolytic activation was negligible before the oxidation, but was significantly accelerated after the oxidation of the alpha-lipoic acid moiety, suggesting an oxidative stimuli-responsive activation of the prodrug. The camptothecin nanoprodrug was found to possess significant inhibitory effect on the proliferation of U87-MG glioma cells with an IC(50) of 20 nM.

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Jan 27, 2009·International Journal of Pharmaceutics·Bong-Seop LeeJohn S Yu
Feb 24, 2009·Bioorganic & Medicinal Chemistry Letters·Bong Seop LeeJohn S Yu

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Citations

Mar 25, 2011·Amino Acids·Marcus A EtienneDavid H Coy
Jan 13, 2015·Experimental and Therapeutic Medicine·Murat PekmezNazli Arda
Nov 15, 2018·Journal of Translational Internal Medicine·Justin S MichaelJohn S Yu
Feb 3, 2013·Biomaterials Science·Zhijian SongXuemei Chen
May 1, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Mohd KhanShahper Khan

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