Photodynamic therapy

This article describes the term of photodynamic therapy, a relatively new way of cancer treatment and gives the rewiev of the commonly used photosensitizers, expecially the phthalocyanines and their way of action. The last part is devoted to the action of PDT on human erythrocytes.Zadanie pt. „Digitalizacja i udostępnienie w Cyfrowym Repozytorium Uniwersytetu Łódzkiego kolekcji czasopism naukowych wydawanych przez Uniwersytet Łódzki” nr 885/P-DUN/2014 dofinansowane zostało ze środków MNiSW w ramach działalności upowszechniającej naukę

Influence of MLS laser radiation on erythrocyte membrane fluidity and secondary structure of human serum albumin

The biostimulating activity of low level laser radiation of various wavelengths and energy doses is widely documented in the literature, but the mechanisms of the intracellular reactions involved are not precisely known. The aim of this paper is to evaluate the influence of low level laser radiation from an multiwave locked system (MLS) of two wavelengths (wavelength = 808 nm in continuous emission and 905 nm in pulsed emission) on the human erythrocyte membrane and on the secondary structure of human serum albumin (HSA). Human erythrocytes membranes and HSA were irradiated with laser light of low intensity with surface energy density ranging from 0.46 to 4.9 J cm(−2) and surface energy power density 195 mW cm(−2) (1,000 Hz) and 230 mW cm(−2) (2,000 Hz). Structural and functional changes in the erythrocyte membrane were characterized by its fluidity, while changes in the protein were monitored by its secondary structure. Dose-dependent changes in erythrocyte membrane fluidity were induced by near-infrared laser radiation. Slight changes in the secondary structure of HSA were also noted. MLS laser radiation influences the structure and function of the human erythrocyte membrane resulting in a change in fluidity

Influence of valoneoyl groups on the interactions between Euphorbia tannins and human serum albumin

Abstract Tannins belonging to plant polyphenols, are large group of compounds with diverse biological activity. Many of them are being studied as potential natural medicine due to their antioxidant, antiviral, antibacterial or anticancer properties. However, so far little is known about the structural and functional relations in protein-tannin interactions, in particularly the role of valoneoyl groups in tannin structure. In this study we first investigated the mechanisms of interaction 1,2-di-O-galloyl-4,6-valoneoyl-β-D-glucose (Tannin 1), 2-O-galloyl-4,6-valoneoyl-β-D-glucose (Tannin 2), 3-O-galloyl-1,2-valoneoyl-β-D-glucose (Tannin 3) isolated from Euphorbia plants with human serum albumin (HSA). To get more detailed information about nature of albumin-tannin interactions besides standard Trp fluorescence quenching analysis we used also transmission electron microscopy (TEM), circular dichroism (CD) and fluorescence labelling (ANS dye) techniques. It was shown that all the tannins strongly interacted with HSA and quenched the tryptophan amino acid (Trp) fluorescence but slightly changed protein secondary structure (circular dichroism CD analysis). TEM demonstrated that all used compounds formed complexes with HSA. Tannin 3 most strongly quenched HSA fluorescence and changed protein dynamic as well as had the highest binding constant (12.4 ± 1.1 × 1013 M−1 s−1 in comparison with 7.0 ± 0.38 × 1013 M−1 s−1 for tannin 1 and 8.6 ± 1.1 × 1013 M−1 s−1 for tannin 2). For tannin 1 that was the largest of the studied compounds was observed the weakest influence on the fluorescence parameters, probably due to the effect of steric hindrancelimiting interaction with albumin Trp pocket. On the other hand T1 induced the strongest changed secondary structure of HSA in comparison to another studied tannins. Our results demonstrated that all used tannins interact with albumin by complex formation but in the manner depends on chemical structure and flexibility of studied compounds

Poly(propylene imine) dendrimers and amoxicillin as dual-action antibacterial agents

Besides acting as antimicrobial compounds, dendrimers can be considered as agents that improve the therapeutic effectiveness of existing antibiotics. In this work we present a new approach to using amoxicillin (AMX) against reference strains of common Gram-negative pathogens, alone and in combination with poly(propylene imine) (PPI) dendrimers, or derivatives thereof, in which 100% of the available hydrogen atoms are substituted with maltose (PPI 100%malG3). The concentrations of dendrimers used remained in the range non-toxic to eukaryotic cells. The results indicate that PPI dendrimers significantly enhance the antibacterial effect of amoxicillin alone, allowing antibiotic doses to be reduced. It is important to reduce doses of amoxicillin because its widespread use in medicine could lead to the development of bacterial resistance and environmental pollution. This is the first report on the combined antibacterial activity of PPI surface-modified maltose dendrimers and amoxicillin

Affecting NF-κB cell signaling pathway in chronic lymphocytic leukemia by dendrimers-based nanoparticles

Abstract The complex genetic diversity of chronic lymphocytic leukemia (CLL) makes it difficult to determine the effective and durable therapy beneficial to patients. During the several past years' significant insights in the biology of the disease and its treatment have been made, allowing for the identification of promising novel therapeutic agents. The investigation of signaling pathways to understand the biological character of CLL together with the development of molecular profiling is key in personalized approach in therapy for this disease. As it was already proven, maltotriose (M3) modified fourth generation poly(propylene imine) dendrimers(PPI-G4) modulate BCR, TRAIL and WNT signaling pathway gene expression in CLL cells and strongly influence their survival by inducing apoptosis and inhibiting proliferation. The aim of this study was to evaluate the influence of PPI-G4-M3 dendrimers on NFκB pathway gene expression in CLL (MEC-1) cells with 60 K microarray, as it is one of the major factors in the pathogenesis of B-cell neoplasms. The findings were compared with those obtained with Fludarabine (FA) and the results indicate that PPI-G4-M3 dendrimers affect the expression of the examined genes and exert comparable effect on the CLL cells to FA. Dendrimers are one of the most potent groups of nanometer-sized macromoleculesfor closing the gap between the present ineffective treatment and the future effective personalized therapy due to their potential versatile biological propertie

Ruthenium metallodendrimer against triple-negative breast cancer in mice

Carbosilane metallodendrimers, based on the arene Ru(II) complex (CRD13) and integrated to imino-pyridine surface groups have been investigated as an anticancer agent in a mouse model with triple-negative breast cancer. The dendrimer entered into the cells efficiently, and exhibited selective toxicity for 4T1 cells. In vivo investigations proved that a local injection of CRD13 caused a reduction of tumour mass and was non-toxic. ICP analyses indicated that Ru(II) accumulated in all tested tissues with a greater content detected in the tumour.European CommissionMinisterio de Economía y CompetitividadComunidad de MadridJunta de Comunidades de Castilla-La Manch

Heterofunctionalized polyphenolic dendrimers decorated with caffeic acid: Synthesis, characterization and antioxidant activity

Dendrimers, branched polymer structures, have been widely studied as efficient drug carriers. Scientists are trying to find new dendrimer-based formulations with the properties needed for biomedical applications such as improved bioavailability, low toxicity and high transfection profiles. The unique drug delivery properties of carbosilane dendrimers have already been demonstrated. Their efficacy has been further improved by conju-gation with polyphenols, plant secondary metabolites with a wide range of biological activities, including antioxidant effects that are beneficial for human health. The present study focuses on synthesis and character-ization of two new types of carbosilane dendritic systems, one family presents one or two caffeic acid units and ammonium groups on the surface to make them water soluble. The other family has, in addition to the two mentioned functionalities, one or two polyethylene glycol (PEG) chains in the structure to increase the biocompatibility of the system. Carbosilane dendrimers with caffeic acid have low toxicity and protect eryth-rocytes against oxidative hemolysis. These dendrimers also decrease AAPH-induced ROS production in human fibroblasts.Various techniques demonstrating such antioxidant activities have been applied in the current research. The best antioxidant properties were shown for the dendrimer with two PEG-caffeic acid moieties. Further aspects of the biochemical characterization of the dendrimers are also considered and discussed.Ministerio de Ciencia e InnovaciónMinisterio de Economía y CompetitividadJunta de Comunidades de Castilla-La ManchaComunidad de MadridPolish National Agency for Academic Exchang

Silver Nanoparticles Surface-Modified with Carbosilane Dendrons as Carriers of Anticancer siRNA

Gene therapy is a promising approach in cancer treatment; however, current methods have a number of limitations mainly due to the difficulty in delivering therapeutic nucleic acids to their sites of action. The application of non-viral carriers based on nanomaterials aims at protecting genetic material from degradation and enabling its effective intracellular transport. We proposed the use of silver nanoparticles (AgNPs) surface-modified with carbosilane dendrons as carriers of anticancer siRNA (siBcl-xl). Using gel electrophoresis, zeta potential and hydrodynamic diameter measurements, as well as transmission electron microscopy, we characterized AgNP:siRNA complexes and demonstrated the stability of nucleic acid in complexes in the presence of RNase. Hemolytic properties of free silver nanoparticles and complexes, their effect on lymphocyte proliferation and cytotoxic activity on HeLa cells were also examined. Confocal microscopy proved the effective cellular uptake of complexes, indicating the possible use of this type of silver nanoparticles as carriers of genetic material in gene therapy. © 2020 by the authors. Licensee MDPI, Basel, Switzerland

In Vitro anticancer properties of copper metallodendrimers

Newly synthesized carbosilane copper dendrimers (CCD) with chloride and nitrate surface groups seem to be good candidates to be used as gene and drug carriers in anti-cancer therapy, due to their properties such as size and surface charge. Copper attached to the nanoparticles is an important element of many biological processes and recently their anti-cancer properties have been widely examined. Zeta size and potential, transmission electron microscopy (TEM), circular dichroism (CD), analysis of haemolytic activity, and fluorescence anisotropy techniques were used to characterize copper dendrimers. Additionally, their cytotoxic properties toward normal (PBMC) and cancer (1301; HL-60) cells were examined. All tested dendrimers were more cytotoxic against cancer cells in comparison with normal cells