The pH-dependent distribution of the photosensitizer chlorin e6 among plasma proteins and membranes: A physico-chemical approach

H. Mojzisova , S. Bonneau , C. Vever-Bizet , D. Brault

Bibtex , URL
Biochim Biophys Acta, 1768, 2, 366-74
Published 01 Feb. 2007
DOI: 10.1016/j.bbamem.2006.10.009
ISSN: 0005-2736


Decrease in interstitial pH of the tumor stroma and over-expression of low density lipoprotein (LDL) receptors by several types of neoplastic cells have been suggested to be important determinants of selective retention of photosensitizers by proliferative tissues. The interactions of chlorin e6 (Ce6), a photosensitizer bearing three carboxylic groups, with plasma proteins and DOPC unilamellar vesicles are investigated by fluorescence spectroscopy. The binding constant to liposomes, with reference to the DOPC concentration, is 6 X 10(3) M-1 at pH 7.4. Binding of Ce6 to LDL involves about ten high affinity sites close to the apoprotein and some solubilization in the lipid compartment. The overall association constant is 5.7 X 10(7) M-1 at pH 7.4. Human serum albumin (HSA) is the major carrier (association constant 1.8 X 10(8) M-1 at pH 7.4). Whereas the affinity of Ce6 for LDL and liposomes increases at lower pH, it decreases for albumin. Between pH 7.4 and 6.5, the relative affinities of Ce6 for LDL versus HSA, and for membranes versus HSA, are multiplied by 4.6 and 3.5, respectively. These effects are likely driven by the ionization equilibria of the photosensitizer carboxylic chains. Then, the cellular uptake of chlorin e6 may be facilitated by its pH-mediated redistribution within the tumor stroma. (c) 2006 Elsevier B.V All rights reserved.

Cette publication est associée à :

Plasticité membranaire et fonctions cellulaires