hypocrellin-b and Neoplasms

Photodynamic therapy (PDT) is a promising new modality in the treatment of cancers, which employs the interaction between a tumor-localizing photosensitizer and light of an appropriate wavelength to bring about molecular oxygen-induced cell death. We have investigated the efficacy of photosensitizers from the family perylenequinone, namely Hypericin, Hypocrellin A and B, in the treatment of cancer. These photosensitizers are known as potent second generation natural photosensitizers that have phototherapeutic advantages over the presently used porphyrins. We have studied the in vitro signaling mechanism involved in the photodynamic action following PDT in various human carcinoma cell lines. The difference of tumor cell death between two modes of action i.e., vascular- and cellular-mediated cell death, were evaluated in order to compare treatments that can efficaciously eradicate tumor in xenografts model. The antivascular effect of PDT was demonstrated in the chick chorioallantoic membrane (CAM) model. Tumor therapy based on targeting the vasculature of the tumor is indeed promising as demonstrated in the higher relative regression percentage of treated tumor compared to cellular targeted PDT. The favorable tumor response derived from short drug-light interval mediated PDT was primarily based on the differential uptake of the photosensitizer into tumor-associated vasculature as opposed to the cellular compartments of the tumor.

Topics: Animals; Anthracenes; Apoptosis; Blood Vessels; Humans; Neoplasms; Perylene; Phenol; Photochemotherapy; Photosensitizing Agents; Quinones

A novel carbon dot-based luminescence probe for singlet oxygen (

Topics: Animals; Anthracenes; Antineoplastic Agents; Carbon; Female; HeLa Cells; Humans; Imidazoles; Luminescence; Luminescent Agents; Methylene Blue; Mice, Inbred BALB C; Mice, Nude; Neoplasms; Perylene; Photochemotherapy; Photosensitizing Agents; Quantum Dots; Quinones; Singlet Oxygen

Topics: Animals; Cell Line, Tumor; Female; Mice; Mice, Nude; Nanoshells; Neoplasms; Optical Imaging; Perylene; Photoacoustic Techniques; Photochemotherapy; Photosensitizing Agents; Polyesters; Polyethylene Glycols; Quinones; Theranostic Nanomedicine

To optimize synergistic cancer therapy, we rationally assemble an inorganic-organic nanocomplex using a folate-modified lipid bilayer spread on photosensitizer-entrapped mesoporous silica nanoparticle (MSN) coated gold nanorods (AuNRs). In this hybrid bioconjugate, the large specific surface area and pore size of AuNR@MSN guarantee a high loading capacity of small photosensitive molecules. The modification with selective mixed liposomes on the surface of AuNR@MSN enables faster cellular internalization and enhancement of endocytosis. Under one-time NIR two-photon illumination, AuNR-mediated hyperthermia can kill cancer cells directly. Meanwhile, the loaded photosensitizer, hypocrellin B, generates two kinds of reactive oxygen species (ROS) to induce cell apoptosis. Remarkably, hyperthermia can improve the yield of ROS. After intravenous injection of this bioconjugate into female BALB/c nude mice followed by laser irradiation (808 nm, 1.3 W cm(-2), 6 min), the tumor growth is suppressed completely. The tumors are not recurrent within the observation time (19 days), and the normal or main organs are not obviously pathological. Thus, such a simplified and selective cancer treatment, combining photothermal and photodynamic therapy in a synergistic manner, provides outstanding efficiency in vivo. This nanocomplex with well-defined core@shell nanostructures integrated with a two-photon technique holds great promise to improve cancer phototherapy with a high efficiency in the clinic.

Topics: Animals; Antineoplastic Agents; Dose-Response Relationship, Drug; Female; Gold; Humans; Hydrolysis; Liposomes; MCF-7 Cells; Metal Nanoparticles; Mice; Mice, Inbred BALB C; Mice, Nude; Microscopy, Confocal; Nanotechnology; Neoplasms; Perylene; Photochemotherapy; Photons; Quinones; Reactive Oxygen Species; Silicon Dioxide

A reactive template method was used to fabricate alginate-based hydrogel microcapsules. The uniform and well-dispersed hydrogel capsules have a high drug loading capacity. After they are coated by a folate-linked lipid mixture on the surface, the capsules possess higher cell uptake efficiency by the molecule recognition between folate and the folate-receptor overexpressed by the cancer cells. Moreover, in this bioconjugate, the lipid could remarkably reduce the release rate of hydrophilic doxorubicin from the hydrogel microcapsules and encapsulate the hydrophobic photosensitizer hypocrellin B. The biointerfaced capsules could be used as drug carriers for combined treatment against cancer cell proliferation in vitro; this was much more effective than chemotherapy or photodynamic therapy alone.

Topics: Alginates; Capsules; Cell Proliferation; Doxorubicin; Drug Carriers; Glucuronic Acid; HeLa Cells; Hexuronic Acids; Humans; Hydrogel, Polyethylene Glycol Dimethacrylate; Neoplasms; Perylene; Photosensitizing Agents; Quinones

The chorioallantoic membrane (CAM) assay is a widely used bioassay in early in vivo cancer research. The CAM allows non-invasive study of in vivo microvasculature and blood circulation. This report describes the first topical application investigation of photodynamic response in the CAM model using Hypericin (HY) and Hypocrellin B (HB) that belongs to the perylenequinone family. Briefly, cultivated carcinoma of the human bladder cell line (MGH), were inoculated on the CAM of fertilized eggs of embryo age (EA) 9. Tumor growth was evaluated by digital stereomicroscopy. Photodynamic therapy (PDT) was performed following topical application of the photosensitizers. We were able to demonstrate that these perylenequinones localized selectively in the xenografted bladder tumor and in the vasculature of the CAM. Photodynamic treatments were performed using a custom-made non-laser light source coupled into a flexible fiber bundle to selectively excite the photosensitizers in order to induce photodamage to the tumor and vasculature. The vascular damage induced was quantitatively measured following topical application of the photosensitizers. Both photosensitizers exhibited very similar degrees of photodamage to the CAM. The CAM model offers an exciting avenue for the study of PDT induced effect on the vasculature. Our preliminary results support that the CAM model could potentially serve as a customized model to study photodynamic therapy effects of various photosensitizers on specific tumor models.

Topics: Animals; Anthracenes; Blood Vessels; Chickens; Chorioallantoic Membrane; Neoplasms; Perylene; Photochemotherapy; Photosensitizing Agents; Quinones

Hypocrellins A and B are pigments which are isolated from the parasitic fungi Hypocrella bambuase sacc and Shiraia bambusicola P. Heen found in the People's Republic of China and other parts of Asia including Sri Lanka. These agents, which belong to the general class of perylene quinonoid pigments, have a long history of traditional medicinal agents especially in Asia. Hypocrellins are under extensive investigation as photosensitizing agents for photodynamic therapy (PDT). Hypocrellin compounds were selected as potential photosensitizers for PDT owing to their high quantum yields of singlet oxygen (1O2), and facility for site-directed chemical modification to enhance phototoxicity, pharmacokinetics, solubility, and light absorption in the red spectral region, among other properties. The cellular uptake, evaluated by spectrofluorimetry and confocal laser scanning microscopy (CLSM) demonstrated that both HA and HB exhibited high and fast uptake and rapid internalization as revealed by their bio-distribution pattern. In addition, the present study employed both immunocytochemical and Western blot techniques to explore the photo-induced expression of apoptosis related proteins in NPC as well as other human carcinoma cells. Using spectrofluorimetry and CLSM we have determined the cellular fluorescence as a marker for the uptake of HA and HB. Co-staining with either HA or HB and fluorescent dyes specific for cell organelles revealed an intracellular localization of HA and HB in lysosomes other than mitochondria.

Topics: Apoptosis; Apoptotic Protease-Activating Factor 1; Bambusa; bcl-2-Associated X Protein; Blotting, Western; Cytochrome c Group; Drugs, Chinese Herbal; Humans; Immunoenzyme Techniques; Lysosomes; Microscopy, Confocal; Mitochondria; Neoplasms; Perylene; Phenol; Photochemotherapy; Photosensitizing Agents; Proteins; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-bcl-2; Quinones; Subcellular Fractions; Tumor Cells, Cultured