phytochlorin and Inflammation

Nanoparticles have been extensively used for inflammation imaging and photodynamic therapy of cancer. However, the major translational barriers to most nanoparticle-based imaging and therapy applications are the limited depth of tissue penetration, inevitable requirement of external irradiation, and poor biocompatibility of the nanoparticles. To overcome these critical limitations, we synthesized a sensitive, specific, biodegradable luminescent nanoparticle that is self-assembled from an amphiphilic polymeric conjugate with a luminescent donor (luminol) and a fluorescent acceptor [chlorin e6 (Ce6)] for in vivo luminescence imaging and photodynamic therapy in deep tissues. Mechanistically, reactive oxygen species (ROS) and myeloperoxidase generated in inflammatory sites or the tumor microenvironment trigger bioluminescence resonance energy transfer and the production of singlet oxygen (

Topics: A549 Cells; Animals; Antineoplastic Agents; Chlorophyllides; Humans; Inflammation; Luminescence; Luminescent Agents; Luminol; Male; MCF-7 Cells; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Nude; Nanoparticles; Neoplasms; Photochemotherapy; Polymers; Porphyrins; RAW 264.7 Cells; Reactive Oxygen Species; Theranostic Nanomedicine; Xenograft Model Antitumor Assays

The present study was designed to evaluate the therapeutic potential of antimicrobial photodynamic therapy (PDT) using chlorin e6 with halogen light against acne bacteria-induced inflammation.. Highly purified chlorin e6 (Ce6), as a second generation photosensitizer, was synthesized from Spirulina chlorophyll. To evaluate the antimicrobial property of Ce6-mediated PDT with halogen light, the broth microdilution method and two-color fluorescence assay were used. The free radicals generated upon irradiating Ce6 with halogen light were measured using 2,7-dichlorofluorescin diacetate. Propionibacterium acnes was intradermally injected into the left ear of the ICR mice, and the anti-inflammatory effect of Ce6-mediated PDT with halogen light was measured by the histological examination. The expressions of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS) as well as pro-inflammatory cytokines were also measured by Western blotting.. Chlorin e6-mediated PDT with halogen light (30,000 lx) inactivated various skin bacteria, including P. acnes in a dose-dependent manner. The MIC99 value against P. acnes (KCTC3314) of Ce6 with light was >0.49 μg/ml, whereas the MIC99 for Ce6 alone was >31.25 μg/ml. Ce6-mediated PDT suppressed the expression of P. acnes-induced pro-inflammatory cytokines and iNOS, but not COX-2 in a mouse model.. This study showed a remarkable therapeutic effect of chlorin e6-mediated PDT with halogen light against P. acnes-induced inflammation. Our results suggest for the first time the potential of Ce6-mediated PDT with halogen light as a more effective and safer alternative treatment to antibiotic therapy against pathogenic infections of the skin.

Topics: Acne Vulgaris; Animals; Blotting, Western; Chlorophyllides; Cyclooxygenase 2; Cytokines; Disease Models, Animal; Dose-Response Relationship, Drug; Gene Expression Regulation; Halogens; Inflammation; Male; Mice; Mice, Inbred ICR; Nitric Oxide Synthase Type II; Photochemotherapy; Porphyrins; Propionibacterium acnes; Radiation-Sensitizing Agents

Mono-L-aspartyl chlorin e6 (Talaporfin sodium) is a novel photosensitizer, and is currently being used in photodynamic therapy for various malignant tumors in combination with irradiation with a 664 nm laser. An interesting characteristic of Talaporfin sodium is that the skin photosensitivity after injection of this agent disappears faster than any other existing photosensitizers. This study examined the vascular events that occurred postirradiation in the chicken comb as a capillary malformation model after photosensitization with Talaporfin sodium.. A single intravenous bolus injections of Talaporfin sodium was administered to the chickens, and a 1 cm diameter area of the comb of each animal was irradiated with a 664 nm visible red laser. The gross changes in the chicken combs were recorded for 7-14 days after photodynamic therapy. For the histological examination, HE, PTAH and Azan stained sections were analyzed.. All treated chicken combs had blanched after photodynamic therapy. Microscopy demonstrated an absence of erythrocytes and the vessel lumina were obliterated, leaving the normal overlying epidermis completely intact. Concomitantly with selective destruction of the capillaries in the target area, moderate invasion of inflammatory cells and a slight increase in the stroma were observed.. In the chicken comb model, photodynamic therapy with Talaporfin sodium effectively achieved selective destruction of the microvasculature while leaving the epidermis intact. Our results strongly suggest that photodynamic therapy with Talaporfin sodium could be a feasible method to treat dermal hypervascular lesions.

Topics: Animals; Capillaries; Chickens; Chlorophyllides; Comb and Wattles; Erythrocytes; Inflammation; Male; Photochemotherapy; Photosensitizing Agents; Porphyrins; Port-Wine Stain; Radiation-Sensitizing Agents; Skin; Skin Diseases