PREFERENTIAL BINDING OF CARBOXYLATE FORM OF CAMTOTHECIN BY HUMAN SERUM ALBUMIN

喜树碱显示出前所未有的抗肿瘤活性

Camptothecin displays unprecedented antitumor activities against human colon cancer. To date its full therapeutic utility has been limited by poor water-solubility and the aqueous instability of the lactone ring moiety. Ring opening is rapid, resulting in a complete loss of biological activity. In published reports, we demonstrate that liposome-bound camptothecin is stable, thus suggesting that liposomes may serve as useful drug delivery systems for solubilizing camptothecin and preserving both its lactone ring and antitumor activity. In order to study the equilibrium association of camptothecin with lipid bilayers, we exploited the drug's intense intrinsic fluorescence. Fluorescence is associated with the extended conjugation of the quinoline ring system. Upon association with small unilamellar vesicles (SUVs) composed of L-`-dimyristoyl phosphatidylglycerol (DMPG), the emission spectra of camptothecin's emission spectrum shifts to lower wavelength, or blue shifts, some 16 nm. These spectral shifts allow the binding constants to be measured.