phytochlorin and Hemolysis

Liposomal technologies are used in order to improve the effectiveness of current therapies or to reduce their negative side effects. However, the liposome-erythrocyte interaction during the intravenous administration of liposomal drug formulations may result in changes within the red blood cells (RBCs). In this study, it was shown that phosphatidylcholine-composed liposomal formulations of Photolon, used as a drug model, significantly influences the transmembrane potential, stiffness, as well as the shape of RBCs. These changes caused decreasing the number of stomatocytes and irregular shapes proportion within the cells exposed to liposomes. Thus, the reduction of anisocytosis was observed. Therefore, some nanodrugs in phosphatidylcholine liposomal formulation may have a beneficial effect on the survival time of erythrocytes.

Topics: Animals; Cell Shape; Chlorophyllides; Drug Compounding; Erythrocytes; Female; Hemolysis; Liposomes; Membrane Potentials; Phosphatidylcholines; Porphyrins; Radiation-Sensitizing Agents; Swine

Surgery combined with adjuvant or neoadjuvant chemotherapy is still the standard treatment for osteosarcoma. However, the high risk of tumor recurrence and side effects of chemotherapy usually lead to high mortality for cancer patients. Herein, the multi-targeted receptor tyrosine kinase (RTK) inhibitor sunitinib (Sun) and photodynamic therapy (PDT) drug chlorin e6 (Ce6) were locally delivered to the postoperative tumor site via a zwitterionic hydrogel. This hydrogel exhibited excellent biocompatibility and redox responsiveness. In vitro study demonstrated that Sun/Ce6@Gel induced 143B human osteosarcoma cell apoptosis via downregulating the expression of Bcl-2 and upregulating the expression levels of Bax and caspase-3. Similarly, the in vivo study showed that Sun/Ce6@Gel provided sustained drug release under redox conditions, and then synergistically induced tumor apoptosis to prevent tumor recurrence without systemic toxicity. Therefore, local implantation of Sun/Ce6@Gel may be a promising topical therapeutic method for prevention of the recurrence of osteosarcoma after surgery.

Topics: Animals; Antineoplastic Agents; bcl-2-Associated X Protein; Biocompatible Materials; Caspase 3; Chlorophyllides; Combined Modality Therapy; Drug Carriers; Drug Compounding; Drug Liberation; Gene Expression Regulation; Hemolysis; Humans; Hydrogels; Male; Mice, Inbred BALB C; Mice, Nude; Neoplasm Recurrence, Local; Osteosarcoma; Photochemotherapy; Photosensitizing Agents; Porphyrins; Proto-Oncogene Proteins c-bcl-2; Sunitinib

It is important to explore effective treatment for liver cancer. Photodynamic therapy (PDT) is a novel technique to treat liver cancer, but its clinical application is obstructed by limited depth of visible light penetration into tissue. The near-infrared (NIR) photosensitizer is a potential solution to the limitations of PDT for deep tumor tissue treatment.. We aimed to investigate 808 nm NIR light-excited UCNPs@mSiO. In our study, 808 nm NIR light-excited upconversion nanoparticles (UCNPs) were simultaneously loaded with the photosensitizer chlorin e6 (Ce6) and the antibody glypican-3 (GPC3), which is overexpressed in hepatocellular carcinoma cells. The multitasking UCNPs@mSiO. We found that the UCNPs@mSiO. We believe that the utilization of 808 nm NIR excited UCNPs@mSiO

Topics: Animals; Antibodies; Cell Line, Tumor; Chlorophyllides; Glypicans; Hemolysis; Hep G2 Cells; Humans; Light; Liver Neoplasms; Male; Mice, Nude; Nanoparticles; Photochemotherapy; Photosensitizing Agents; Porphyrins; Xenograft Model Antitumor Assays

In the present work, we investigated the dark and photoinduced cytotoxic activity of the new chlorophyll-a derivatives which contain the substituents of oligoethylene glycol on the periphery of their macrocycles. These compounds were tested using human cell lines to estimate their potential as photosensitizers for photodynamic therapy of cancer. It was shown that all the tested compounds have expressed photoinduced cytotoxic activity in vitro. Detailed study of the biological activity of one of the most perspective compound in this series-pyropheophorbide-a 17-diethylene glycol ester (Compound

Topics: A549 Cells; Animals; Apoptosis; Cell Line; Cell Survival; Chlorophyll; Chlorophyllides; Comet Assay; Darkness; DNA Damage; Dose-Response Relationship, Drug; Gene Expression; HEK293 Cells; HeLa Cells; Hemolysis; Humans; Inhibitory Concentration 50; Light; Mice; Microscopy, Fluorescence; Molecular Structure; Photosensitizing Agents; Polyethylene Glycols; Porphyrins

Photodynamic tumor-destroying activity of the boronated chlorin e6 derivative BACE (chlorin e6 13(1)-N-{2-[N-(1-carba-closo-dodecaboran-1-yl)methyl]aminoethyl}amide-15(2), 17(3)-dimethyl ester), previously described in Moisenovich et al. (2010) PLoS ONE 5(9) e12717, was shown here to be enormously higher than that of unsubstituted chlorin e6, being supported by the data on much higher photocytotoxicity of BACE in M-1 sarcoma cell culture. To validate membrane damaging effect as the basis of the enhanced tumoricidal activity, BACE was compared with unsubstituted chlorin e6 in the potency to photosensitize dye leakage from liposomes, transbilayer lipid flip-flop, inactivation of gramicidin A ionic channels in planar lipid membranes and erythrocyte hemolysis. In all the models comprising artificial and cellular membranes, the photodynamic effect of BACE exceeded that of chlorin e6. BACE substantially differed from chlorin e6 in the affinity to liposomes and erythrocytes, as monitored by fluorescence spectroscopy, flow cytometry and centrifugation. The results support the key role of membrane binding in the photodynamic effect of the boronated chlorin e6 amide.

Topics: Amides; Animals; Boron; Cell Membrane; Cells, Cultured; Chlorophyllides; Erythrocytes; Female; Flow Cytometry; Hemolysis; Humans; Light; Lipid Bilayers; Liposomes; Membranes, Artificial; Photosensitizing Agents; Porphyrins; Rats; Sarcoma

The relationships between the rate of post-irradiated photohaemolysis sensitized by chlorin e6 and parameters such as the light fluence (time of irradiation) and sensitizer concentration were studied. On the basis of the single-parametric approach proposed by Valenzeno and Pooler, it was found that the haemolytic rate varies with the square of both the light fluence and the sensitizer concentration. Thus it can be concluded that, in a single erythrocyte lesion, two chlorin e6 molecules participate, each absorbing one photon. The possibility of suppression of post-irradiation haemolysis was also studied using the lipophilic antioxidant, butylated hydroxytoluene (BHT), and scavengers of 1O2, O2.- and HO. radicals. It was found that BHT inhibits, to a considerable extent, the post-irradiation lysis of cells, by about a factor of 2.5 at a BHT concentration of 9 microM. The addition to the medium of NaN3 (a scavenger of 1O2), superoxide dismutase (a scavenger of O2.- radicals), ethanol and D-mannitol (scavengers of HO. radicals), when irradiation was interrupted, did not produce a marked influence on the kinetics of subsequent haemolysis. On the basis of the results obtained, the nature of erythrocyte targets, which are crucial for the photodynamic effect of chlorin e6, is discussed.

Topics: Biological Transport; Chlorophyllides; Erythrocytes; Hemolysis; Humans; In Vitro Techniques; Kinetics; Light; Porphyrins; Radiation-Sensitizing Agents