Recombinant high density lipoprotein reconstituted with apolipoprotein AI cysteine mutants as delivery vehicles for...

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 to be primarily spherical model with mean diameter were 22.39±10.25nm, 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.