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

International Journal of Molecular Sciences

Tatyana E. Zorina¹  Vladimir P. Zorin¹  Marina V. Mal’shakova²  Dmitry V. Belykh²  Dmitry R. Karimov³  Dmitry B. Berezin³  Olga V. Shukhto³  Tatyana V. Kustova³  Nataliya L. Smirnova⁴  Philipp K. Morshnev⁴  Andrey V. Kustov⁴  Natal’ya V. Kukushkina⁴ 

[1] Department of Biophysics, Belarussian State University (BSU), 220030 Minsk, Belarus;Institute of Chemistry of the Komi Science Centre of the Ural Branch of Russian Academy of Sciences (ICKSC UB RAS), 167000 Syktyvkar, Russia;Institute of Macroheterocyclic Compounds, Ivanovo State University of Chemistry and Technology (ISUCT), 153012 Ivanovo, Russia;United Physicochemical Centre of Solutions, G.A. Krestov Institute of Solution Chemistry, Russian Academy of Sciences (ISC RAS), 153045 Ivanovo, Russia;

关键词: photodynamic therapy;    chlorin photosensitizers;    1-octanol/phosphate saline buffer partition;    solvation;    singlet oxygen generation;    photoinactivation;   

DOI  :  10.3390/ijms23105294

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown