Photodynamic activity of the boronated chlorin e6 amide in artificial and cellular membranes

Abstract

Photodynamic tumor-destroying activity of the boronated chlorin e6 derivative BACE (chlorin e6 13(1)-N-{2-[N-(1-carba-closo-dodecaboran-1-yl)methyl]aminoethyl}amide-15(2), 17(3)-dimethyl ester), previously described in Moisenovich et al. (2010) PLoS ONE 5(9) e12717, was shown here to be enormously higher than that of unsubstituted chlorin e6, being supported by the data on much higher photocytotoxicity of BACE in M-1 sarcoma cell culture. To validate membrane damaging effect as the basis of the enhanced tumoricidal activity, BACE was compared with unsubstituted chlorin e6 in the potency to photosensitize dye leakage from liposomes, transbilayer lipid flip-flop, inactivation of gramicidin A ionic channels in planar lipid membranes and erythrocyte hemolysis. In all the models comprising artificial and cellular membranes, the photodynamic effect of BACE exceeded that of chlorin e6. BACE substantially differed from chlorin e6 in the affinity to liposomes and erythrocytes, as monitored by fluorescence spectroscopy, flow cytometry and centrifugation. The results support the key role of membrane binding in the photodynamic effect of the boronated chlorin e6 amide.

Carboranyl-Chlorin e6 as a Potent Antimicrobial Photosensitizer

“…Here, we for the first time applied boronated chlorin e 6 amide (BACE, chlorin e 6 13(1)-N-{2-[N-(1-carba-closo-dodecaboran-1-yl)methyl]aminoethyl}amide-15(2), 17(3)-dimethyl ester) [ 8 , 9 ] for aPDI and found this photosensitizer to show much higher efficacy against Gram-positive than against Gram-negative bacteria.…”

Unsaturated lipids protect the integral membrane peptide gramicidin A from singlet oxygen

“…The sodium salt of BACE, synthesized as described earlier [33], was a gift from V.A.Ol'shevskaya (Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences). Chlorin e 6 was obtained from Porphyrin Products (Logan, UT).…”

“…Based on the phenomenon of gA photodynamic inactivation, we developed a technique for estimating the photosensitizing and antioxidant efficacy through measurement of the degree of photodynamic inactivation of gA channels in planar bilayer lipid membranes (BLM) [24–30]. Bearing in mind the reduction of radiolytic inactivation of gA in unsaturated lipids [31], here we studied the effect of the double bond content on the gA photodynamic inactivation sensitized by the boronated chlorin e 6 derivative BACE (chlorin e 6 13(1)‐N‐{2‐[N‐(1‐carba‐closo‐dodecaboran‐1‐yl)methyl]aminoethyl}amide‐15(2), 17(3)‐dimethyl ester) – a recently found, very effective agent for PDT [32,33], and compared the results with the corresponding influence of unsaturated lipids on gA channels in the case of the t ‐BOOH addition.…”

Photodynamic inactivation of gramicidin channels in bilayer lipid membranes: Protective efficacy of singlet oxygen quenchers depends on photosensitizer location

“…This model system proved very useful for ana lyzing different properties of photosensitizers [17 21]. We recently showed that unsaturated lipids protect the gram icidin A peptide from photodynamic damage in the pres ence of boronated chlorin e 6 derivative (BACE [22]) and that the degree of protection increases with increasing number of double bonds in the lipid [23]. In this work, we studied the dependence of unsaturated lipid and ascor bate antioxidant activity on the photosensitizer mem brane immersion depth through the example of grami cidin photoinactivation in planar bilayer lipid membrane (BLM).…”