Increased binding of chlorin e(6) to lipoproteins at low pH values

It is well known that the extracellular pH in tumors is lower than that of normal tissue. This has been proposed to be one of the reasons for the tumo r selective uptake of several photosensitizers. Photosensitizers like chlor in e(6) are bound to blood components and delivered to different sites in t he organism. Thus, the effect of pH on their interaction with human plasma needs to be studied in order to understand a possible role of the acidic mi croenvironment in tumors for the drug distribution. Increasing amounts of h uman plasma in the sample resulted in a gradual red shift of the fluorescen ce emission maxima of chlorin es, indicating binding of the drug to some of the plasma components. Titration showed that the drug-plasma interaction w as pH-dependent. The titration curve had an inflection point at 7.4 +/- 0.1 . The relative distribution of the drug among plasma components, as found a fter ultracentrifugation of chlorin eb-doped plasma in a salt gradient, sho wed more binding of the drug to nonlipoproteins than to lipoprotein classes at both pH values studied (6.5 and 7.4). A decrease in the pH was connecte d with a significant increase in drug-lipoprotein binding. The pH of the en vironment affects chlorin e(6)-plasma interaction and the distribution of t he drug among different plasma components. The results of this study indica te a possible role of the acidic microenvironment in tumors for the prefere ntial uptake and retention of several photosensitiziers. (C) 2000 Elsevier Science Ltd. All rights reserved.