Solvation, Cancer Cell Photoinactivation and the Interaction of Chlorin Photosensitizers with a Potential Passive Carrier Non-Ionic Surfactant Tween 80

Abstract

Cancer and drug-resistant superinfections are common and serious problems afflicting millions worldwide. Photodynamic therapy (PDT) is a successful and clinically approved modality used for the management of many neoplastic and nonmalignant diseases. The combination of the light-activated molecules, so-called photosensitizers (PSs), with an appropriate carrier, is proved to enhance PDT efficacy both in vitro and in vivo. In this paper, we focus on the solvation of several potential chlorin PSs in the 1-octanol/phosphate saline buffer biphasic system, their interaction with non-ionic surfactant Tween 80 and photoinactivation of cancer cells. The chlorin conjugates containing D-galactose and L-arginine fragments are found to have a much stronger affinity towards a lipid-like environment compared to ionic chlorins and form molecular complexes with Tween 80 micelles in water with two modes of binding. The charged macrocyclic PSs are located in the periphery of surfactant micelles near hydrophilic head groups, whereas the D-galactose and L-arginine conjugates are deeper incorporated into the micelle structure occupying positions around the first carbon atoms of the hydrophobic surfactant residue. Our results indicate that both PSs have a pronounced affinity toward the lipid-like environment, leading to their preferential binding to low-density lipoproteins. This and the conjugation of chlorin e6 with the tumor-targeting molecules are found to enhance their accumulation in cancer cells and PDT efficacy.