tetra(4-n-methylpyridyl)porphine and Disease-Models--Animal

Photodynamic therapy (PDT) has been applied in clinical cancer treatment. Here we report an aptamer-functionalized nanoscale metal-organic framework for targeted PDT. Our nanosystem can be easily prepared and successfully used for targeted PDT with a significantly enhanced therapeutic efficacy

Topics: Animals; Aptamers, Nucleotide; Cell Survival; Disease Models, Animal; Drug Carriers; Drug Stability; G-Quadruplexes; HeLa Cells; Heterografts; Humans; Metal-Organic Frameworks; Mice; Molecular Targeted Therapy; Neoplasm Transplantation; Neoplasms, Experimental; Photochemotherapy; Photosensitizing Agents; Porphyrins; Treatment Outcome

The fungus Candida albicans commonly causes mucosal and cutaneous infections in patients with impaired immunity. We investigated the effectiveness of the photosensitizer meso-tetra (N-methyl-4-pyridyl) porphine tetra tosylate (TMP-1363) in the photodynamic treatment (PDT) of C. albicans infection in vitro and its selectivity in an animal model.. The efficacy of TMP-1363 in PDT of C. albicans in vitro was compared to that of methylene blue (MB) using a colony forming unit (CFU) assay. In vivo infection in the mouse was established by inoculation of C. albicans yeast in the intradermal space of the ear pinna. Two days post-infection, 0.3 mg ml(-1) TMP-1363 was administered topically. Thirty minutes after TMP-1363 application, the ears were irradiated at 514 nm using a fluence of 90 J cm(-2) delivered at an irradiance of 50 mW cm(-2) . The ears were excised 2 hours post-irradiation, homogenized, and the organism burden was determined by a CFU assay. In vivo wide field and confocal fluorescence imaging assessed the localization of the photosensitizer in relationship to C. albicans.. Photosensitization with TMP-1363 resulted in a greater than three-log increase in killing of C. albicans in vitro compared to MB. In vivo fluorescence imaging demonstrated a high degree of selective labeling of C. albicans by TMP-1363. PDT of infection using TMP-1363 resulted in a significant reduction in CFU/ear relative to untreated controls. Infected ears subjected to PDT displayed complete healing over time with no observable damage to the pinna.. Our in vitro and in vivo findings support TMP-1363-mediated PDT as a viable therapeutic approach for the PDT of candidiasis.

Topics: Administration, Topical; Animals; Candida albicans; Candidiasis; Colony Count, Microbial; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Fluoroscopy; In Vitro Techniques; Methylene Blue; Mice; Mice, Inbred BALB C; Photochemotherapy; Photosensitivity Disorders; Photosensitizing Agents; Porphyrins; Random Allocation; Sensitivity and Specificity