Recombinant high density lipoprotein reconstituted with apolipoprotein AI cysteine mutants as delivery vehicles for 10-hydroxycamptothecin》.pdf

Cancer Letters 298 (2010) 26–33 Contents lists available at ScienceDirect Cancer Letters journal homepage: /locate/canlet Recombinant high density lipoprotein reconstituted with apolipoprotein AI cysteine mutants as delivery vehicles for 10-hydroxycamptothecin Xinbo Zhang, Baosheng Chen * National Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, PR China a r t i c l e i n f o a b s t r a c t Article history: 10-Hydroxycamptothecin (HCPT) is an effective anticancer agent whose therapeutic poten- Received 9 April 2010 tial is limited by poor water-solubility and selectivity, short half-life and side effects. It has Received in revised form 27 May 2010 been shown that high density lipoprotein (HDL) or recombinant HDL (rHDL) reconstituted Accepted 31 May 2010 with wide-type apolipoprotein AI (apoAIwt) is an effective drug delivery model because of its specific structural characteristics and the targeted receptor-mediated uptake mecha- nism. In this study, the apoAIMilano (apoAIM) mutant with higher receptor affinity was cho- Keywords: sen as a potential delivery vehicle from seven cysteine mutants of apoAI constructed by our Apolipoprotein AI laboratory. rHDL–HCPT nanoparticles reconstitu