zn(ii)-phthalocyanine and Lung-Neoplasms

Worldwide, lung cancer remains one of the leading cancers with increasing mortality rates. Though chemotherapy for lung cancer is effective, it is always accompanied by unavoidable and grave side effects. Photodynamic therapy (PDT), using novel photosensitizers, is an advanced treatment method with relatively few side effects. Plant products are emerging as potent photosensitizers (PSs). The dose-dependent effect of Catechin (CA) (20-100 µM) on cellular morphological changes, cell viability, cytotoxicity, proliferation, DNA damage and apoptosis were studied on A549 adenocarcinoma alveolar basal epithelial cells. The effect of CA, along with Zinc phthalocyanine PS at 680 nm and 5 J/cm

Topics: A549 Cells; Antineoplastic Agents; Apoptosis; Catechin; Cell Proliferation; DNA Damage; Dose-Response Relationship, Drug; Drug Synergism; Humans; Indoles; Isoindoles; Lung Neoplasms; Organometallic Compounds; Photochemotherapy; Photosensitizing Agents; Reactive Oxygen Species; Zinc Compounds

Hay synthesis of a novel series of symmetrically tetra-substituted thiophenyl zinc(II)phthalocyanines (RS)

Topics: A549 Cells; Adenocarcinoma; Adenocarcinoma of Lung; Antineoplastic Agents; Carcinoma, Hepatocellular; Cell Line, Tumor; Cell Proliferation; Drug Screening Assays, Antitumor; Fibroblasts; Humans; Indoles; Inhibitory Concentration 50; Isoindoles; Lung Neoplasms; MCF-7 Cells; Molecular Structure; Organometallic Compounds; Structure-Activity Relationship; Zinc Compounds

It is generally accepted that compounds of nanomolecular size penetrate into cells by different endocytic processes. The vehiculization strategy of a compound is a factor that could determine its uptake mechanism. Understanding the influence of the vehicle in the precise mechanism of drug penetration into cells makes possible to improve or modify the therapeutic effects. In this study, using human A-549 cells, we have characterized the possible internalization mechanism of the photosensitizer Zn(II)-phthalocyanine (ZnPc), either dissolved in dimethylformamide (ZnPc-DMF) or included in liposomes of dipalmitoyl-phosphatidyl-choline. Specific inhibitors involved in the main endocytic pathways were used. Co-incubation of cells with ZnPc-liposomes and dynasore (dinamin-mediated endocytosis inhibitor) resulted in a significant decrease of photodamage, whereas other inhibitors did not alter the photodynamic effect of ZnPc. On the contrary, cells treated with ZnPc-DMF in the presence of dynasore, genistein (caveolin-mediated endocytosis inhibitor) or cytochalasin D (macropinocytosis and caveolin-mediated endocytosis inhibitor) showed a significant decrease in ZnPc uptake and photodynamic damage. These results suggest that ZnPc-DMF penetrates into cells mainly by caveolin-mediated endocytosis, whereas ZnPc-liposomes are internalized into cells preferentially by clathrin-mediated endocytosis. We conclude that using different drug vehiculization systems, it is possible to modify the internalization mechanism of a therapeutic compound, which could be of great interest in clinical research.

Topics: Caveolins; Cell Line, Tumor; Cell Membrane; Cell Shape; Cell Survival; Clathrin; Cytochalasin D; Endocytosis; Genistein; Humans; Hydrazones; Indoles; Isoindoles; Liposomes; Lung Neoplasms; Organometallic Compounds; Photochemotherapy; Photosensitizing Agents; Time Factors; Zinc Compounds

Upconverting nanoparticles (UCNPs) have attracted considerable attention as potential photosensitizer carriers for photodynamic therapy (PDT) in deep tissues. In this work, a new and efficient NIR photosensitizing nanoplatform for PDT based on red-emitting UCNPs is designed. The red emission band matches well with the efficient absorption bands of the widely used commercially available photosensitizers (Ps), benefiting the fluorescence resonance energy transfer (FRET) from UCNPs to the attached photosensitizers and thus efficiently activating them to generate cytotoxic singlet oxygen. Three commonly used photosensitizers, including chlorine e6 (Ce6), zinc phthalocyanine (ZnPc) and methylene blue (MB), are loaded onto the alpha-cyclodextrin-modified UCNPs to form Ps@UCNPs complexes that efficiently produce singlet oxygen to kill cancer cells under 980 nm near-infrared excitation. Moreover, two different kinds of drugs are co-loaded onto these nanoparticles: chemotherapy drug doxorubicin and PDT agent Ce6. The combinational therapy based on doxorubicin (DOX)-induced chemotherapy and Ce6-triggered PDT exhibits higher therapeutic efficacy relative to the individual means for cancer therapy in vitro.

Topics: alpha-Cyclodextrins; Animals; Chlorophyllides; Fluorescence Resonance Energy Transfer; Humans; Indoles; Isoindoles; Lung Neoplasms; Mice; Nanoparticles; Organometallic Compounds; Photochemotherapy; Photosensitizing Agents; Porphyrins; Rats; Singlet Oxygen; Zinc Compounds

In this study, zinc phthalocyanine (ZnPc) was loaded onto poly-ɛ-caprolactone (PCL) nanoparticles (NPs) using a solvent emulsification-evaporation method. The process yield and encapsulation efficiency were 74.2% ± 1.2% and 67.1% ± 0.9%, respectively. The NPs had a mean diameter of 187.4 ± 2.1 nm, narrow distribution size with a polydispersity index of 0.096 ± 0.004, zeta potential of -4.85 ± 0.21 mV, and spherical shape. ZnPc has sustained release, following Higuchi's kinetics. The photobiological activity of the ZnPc-loaded NPs was evaluated on human lung adenocarcinoma A549 cells. Cells were incubated with free ZnPc or ZnPc-loaded NPs for 4 h and then washed with phosphate-buffered saline. Culture medium was added to the wells containing the cells. Finally, the cells were exposed to red light (660 nm) with a light dose of 100 J/cm(2). The cellular viability was determined after 24 h of incubation. ZnPc-loaded NPs and free photosensitizer eliminated about 95.9% ± 1.8% and 28.7% ± 2.2% of A549 cells, respectively. The phototoxicity was time dependent up to 4 h and concentration dependent at 0-5 μg ZnPc. The cells viability decreased with the increase of the light dose in the range of 10-100 J/cm(2). Intense lysis was observed in the cells incubated with the ZnPcloaded NPs and irradiated with red light. ZnPc-loaded PCL NPs are the release systems that promise photodynamic therapy use.

Topics: Adenocarcinoma; Cell Line, Tumor; Cell Survival; Drug Delivery Systems; Humans; Indoles; Isoindoles; Lung Neoplasms; Nanomedicine; Nanoparticles; Organometallic Compounds; Photochemotherapy; Photosensitizing Agents; Polyesters; Zinc Compounds

The uptake and selective accumulation of fluorescent labels and drugs into organelles of cultured cells currently are widely investigated in biomedical research. In such studies, co-localization procedures are frequently used to identify the accumulation sites of compounds with biological activity. A drawback with fluorescent labeling is the autofluorescence of some cell organelles, which can hinder the precise assessment of co-localization. We report here labeling of the Golgi apparatus of A-549 cells using the photosensitizer zinc(II)-phthalocyanine (ZnPc) and co-localization with the Golgi probe NBD C6-ceramide. The blue autofluorescence signal of mitochondria can be subtracted easily from the original picture by image processing, after which the co-localization of the isolated red ZnPc signal with the green signal from the Golgi probe is considerably improved.

Topics: 4-Chloro-7-nitrobenzofurazan; Cell Line, Tumor; Ceramides; Contrast Media; Humans; Image Enhancement; Image Interpretation, Computer-Assisted; Indoles; Isoindoles; Lung Neoplasms; Microscopy, Fluorescence; Organometallic Compounds; Photosensitizing Agents; Staining and Labeling; Subtraction Technique; Zinc Compounds

Photodynamic therapy applied to cell cultures represents a widely accepted experimental method to investigate molecular mechanisms that lead to apoptotic cell death. In this context the subcellular localization of photosensitizers seems to be a significant factor in order to determine the apoptotic pathway that could be activated. We have characterized the experimental conditions that induce apoptotic cell death in A-549 cells incubated with ZnPc and irrradiated with red light. Previously we have found that in this cell line the drug is localized in the Golgi apparatus after 3-h incubation. Indirect immunofluorescence analysis of the events that lead to apoptosis made possible the detection of caspase-2 activation in the Golgi region immediately after photodynamic treatments. A few minutes later, the morphology of this organelle starts to disrupt and just 6 h after treatment the nuclei appear affected showing the fragmented appearance typical of apoptotic cell death. From this results we assume that following the photodynamic treatment of A-549 cells with ZnPc, the activation of caspase-2 in the Golgi apparatus could begin to initiate immediately the apoptotic process.

Topics: Adenocarcinoma; Apoptosis; Caspase 2; Caspases; Cell Line, Tumor; Cell Survival; Humans; Indoles; Isoindoles; Lung Neoplasms; Organelles; Organometallic Compounds; Photochemotherapy; Photosensitizing Agents; Zinc Compounds