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

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.

Monocationic Chlorin as a Promising Photosensitizer for Antitumor and Antimicrobial Photodynamic Therapy.

Cancer is one of the leading causes of death worldwide. Despite substantial progress in the understanding of tumor biology, and the appearance of new generations of targeted drugs and treatment techniques, the success achieved in this battle, with some notable exceptions, is still only moderate. Photodynamic therapy (PDT) is a successful but still underestimated therapeutic modality for treating many superficial cancers. In this paper, we focus on the extensive investigation of the monocationic chlorin photosensitizer (PS), considered here as a new photosensitizing agent for both antitumor and antimicrobial PDT. This monocationic chlorin PS (McChl) obtained from methylpheophorbide a (MPh) via a two-step procedure is well soluble in water in the physiological temperature range and forms stable complexes with passive carriers. McChl generates singlet oxygen with a good quantum yield in a lipid-like environment and binds mainly to low- and high-density lipoproteins in a vascular system. A comparison of the photodynamic activity of this agent with the activity of the well-established photosensitizer chlorin e6 (Chl e6) clearly indicates that McChl provides a much more efficient photoinactivation of malignant and microbial cells. The pilot PDT treatment of M1 sarcoma-bearing rats with this PS demonstrates its good potential for further preclinical investigations.

Modulation of Temoporfin Distribution in Blood by ß-Cyclodextrin Nanoshuttles.

Photodynamic therapy represents a more targeted and less invasive alternative cancer treatment to traditional modalities. Temoporfin, as with many photosensitizers, is given by injection into a vein, and its subsequent fate is largely determined by the binding to plasma proteins and interaction with endothelial and blood cells. Thus, it is essential to be able to control and to alter the biodistribution of temoporfin in blood. In the present study, we evaluated the effect of co-administration of temoporfin with randomly methylated ß-CD (Me-ß-CD) on the distribution of temoporfin in the main subpopulations of blood cells of healthy donors using absorbance spectrophotometry and flow cytometry. We showed that cell-bound temoporfin fraction in blood strongly depends on the concentration of Me-ß-CD. In fact, the accumulation of temoporfin in white blood cells was more sensitive than that in red blood cells, due to the higher volume of membranous organelles in white blood cells. Finally, we demonstrated that Me-ß-CD significantly increases cellular uptake of temoporfin cancer human Burkitt's lymphoma Raji cells. The presence of Me-ß-CD resulted in a spotted pattern of temoporfin distribution in the plasma membrane compartment. Our results clearly demonstrated that ß-CDs derivatives provide new options to modulate temoporfin biodistribution in blood.

Unusual photoinduced response of mTHPC liposomal formulation (Foslip).

Liposomal formulations of meso-tetra(hydroxyphenyl)chlorin (mTHPC) have already been proposed with the aim to optimize photodynamic therapy. Spectral modifications of these compounds upon irradiation have not yet been investigated. The objective of this study was to evaluate photobleaching properties of mTHPC encapsulated into dipalmitoylphosphatidylcholine (DPPC) liposomes, Foslip. Fluorescence measurements in DPPC liposomes with different DPPC:mTHPC ratios demonstrated a dramatic decrease in fluorescence anisotropy with increasing local mTHPC concentration, thus suggesting strong interactions between mTHPC molecules in lipid bulk medium. Exposure of Foslip suspensions to small light doses (<50 mJ/cm(2)) resulted in a substantial drop in fluorescence, which, however, was restored after addition to the sample of a non-ionic surfactant Triton X-100. We attributed this behavior to photoinduced fluorescence quenching. This effect depended strongly on the molar DPPC:mTHPC ratio and was revealed only for high local mTHPC concentrations. The results were interpreted supposing energy migration between closely located mTHPC molecules with its subsequent dissipation by the molecules of photoproduct acting as excitation energy traps. We further assessed the effect of photoinduced quenching in plasma protein solution. Relatively slow kinetics of photoinduced Foslip response during incubation in the presence of proteins was attributed to mTHPC redistribution from liposomal formulations to proteins. Therefore, changes in mTHPC distribution pattern in biological systems would be consistent with changes in photoinduced quenching and would provide valuable information on mTHPC interactions with a biological environment.