Self-assembling Peptide As A Carrier For Hydrophobic Anticancer Drug Combretastatin A4 And Application

Combretastatin A4 is one of the most potent low-molecular-weight-disrupting agents(VDAs), which binds to tubulin and targets existing tumor blood vessels. Combretastatin A4 (CA4) is one of the most effective anti-angiogenic drugs in clinical trials. CA4 also showed strong cytotoxicity and can skills a wide variety of cancer cells,such as Hela cells, A549 cells. MCF-7 cells. MKN-45 cells、CFPAC-1 cells、 Hs746T cells、MR32 cells and HL-60 cells. However, the poor water solubility of CA4 and the resulting limited bioavailability significantly impair its antitumor activity. It has been found that ionic complementary self-assembling peptide EAK-II can stabilize hydrophobic anticancer drug CA4 in aqueous solution and also be able to significantly improve the solubility of CA4. The peptides could self-assemble into a stable nanostructures by non-covalent bond with some physical and chemical properties in aqueous solution. CA4 could be entrapped by hydrophobic side by the peptide for vivo delivery. The diameter of EAK-CA4 is about 300 nm. In vitro release studies showed that EAK-CA4 complexes could be released in a sustained manner for 24 h and a higher peptide concentration has a slower release process. In vitro cellular uptake studies demonstrated that EAK-CA4 has a better cell cytotoxic than CA4 and different molecular ratio of EAK-CA4 can also affect the cytotoxicity. These result suggested that the self-assembling peptide may work as a delivery vehicles for hydrophobic anticancer drug to improve its bioavailability, enhance its anti-tumor activity and reduce side effects of drugs.