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Differential interactions of a biological photosensitizer with liposome membranes having varying surface charges

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Abstract

The present work demonstrates the interaction of promising cancer cell photosensitizer, harmane (HM), with liposome membranes of varying surface charges, dimyristoyl-l-a-phosphatidylcholine (DMPC) and dimyristoyl-l-a-phosphatidylglycerol (DMPG). Electrostatic interaction of the cationic probe (HM) with the surface charges of the lipids is responsible for differential modulation of the spectral properties of the drug in different lipid environments. Estimation of partition coefficient (Kp (±10%) = 5.58 × 104 in DMPC and 3.28 × 105 in DMPG) of HM between aqueous buffer and lipid phases reflect strong binding interaction of the drug with both the lipids. Evidence for greater degree of partitioning of HM into DMPG membrane compared to DMPC membrane has been deduced and further substantiated from experimental studies such as steady-state fluorescence anisotropy, micropolarity determination. The molecular modeling investigation by docking simulation coupled with fluorescence quenching experiment has been exploited to substantiate the location of drug at the lipid head-group region. Modulation of the dynamical properties of the drug within the lipid environments has also been addressed. Rotational relaxation dynamics studies unravel the impartation of a significant degree of motional restriction on the probe molecule within the lipids and reinforce the differential interactions of HM with the two lipid systems along the lines of other findings. Fluorescence kinetics studies reveal a faster association (in terms of apparent rate constants describing the process of interaction) of the drug with DMPG membrane compared to DMPC. This result is argued in connection with the electrostatic interaction between the drug and the liposome surface charges.

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  1. Department of Chemistry, University of Calcutta, 92 A. P. C. Road, Calcutta, 700009, India

    Bijan Kumar Paul & Nikhil Guchhait

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Paul, B.K., Guchhait, N. Differential interactions of a biological photosensitizer with liposome membranes having varying surface charges. Photochem Photobiol Sci 11, 661–673 (2012). https://doi.org/10.1039/c2pp05346b

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