Journal
CANCER LETTERS
Volume 298, Issue 1, Pages 26-33Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2010.05.023
Keywords
Apolipoprotein AI; Cysteine mutant; High density lipoprotein; Delivery vehicle; Anticancer
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Funding
- National Basic Research Grant 973 of China [2006CB503801]
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10-Hydroxycamptothecin (HCPT) is an effective anticancer agent whose therapeutic potential is limited by poor water-solubility and selectivity, short half-life and side effects. It has been shown that high density lipoprotein (HDL) or recombinant HDL (rHDL) reconstituted with wide-type apolipoprotein AI (apoAIwt) is an effective drug delivery model because of its specific structural characteristics and the targeted receptor-mediated uptake mechanism. In this study, the apoAI(Milano) (apoAI(M)) mutant with higher receptor affinity was chosen as a potential delivery vehicle from seven cysteine mutants of apoAI constructed by our laboratory. rHDL-HCPT nanoparticles reconstituted with apoAI(M), named as rHDL(M)-HCPT, seemed robe primarily spherical model with mean diameter were 22.39 +/- 10.25 nm, which is similar with the diameter of natural HDL. rHDL(M)-HCPT showed a very steady sustained release pattern in vitro and increased the drug concentration in major organs, relative to free HCPT. Furthermore, in comparison with free HCPT, rHDL(M)-HCPT nanoparticles increased the cytotoxicity of HCPT by 70 and 50 times in SKOV-3 and HCT-116 cells. The data presented in this study indicate that rHDL(M) reconstituted with apoAI(M) could be exploited as a potential delivery vehicle of HCPT with controlled release, enhanced tissue distribution and higher cytotoxicity. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
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