Smruti Pushalkar1, Goutam Ghosh2, QianFeng Xu3, Yang Liu4,5, Ashwini A Ghogare2,5, Cecilia Atem1, Alexander Greer2,5,3, Deepak Saxena1, Alan M Lyons4,5,3. 1. Department of Basic Sciences and Craniofacial Biology , New York University College of Dentistry , New York 10010 , United States. 2. Department of Chemistry , Brooklyn College, City University of New York , Brooklyn , New York 11210 , United States. 3. SingletO2 Therapeutics LLC , 215 W 125th Street, 4th Floor , New York , New York 10027 , United States. 4. Department of Chemistry, College of Staten Island , City University of New York , Staten Island , New York 10314 , United States. 5. Ph.D. Program in Chemistry , The Graduate Center of the City University of New York , 365 Fifth Avenue , New York , New York 10016 , United States.
Abstract
Singlet oxygen is a potent agent for the selective killing of a wide range of harmful cells; however, current delivery methods pose significant obstacles to its widespread use as a treatment agent. Limitations include the need for photosensitizer proximity to tissue because of the short (3.5 μs) lifetime of singlet oxygen in contact with water; the strong optical absorption of the photosensitizer, which limits the penetration depth; and hypoxic environments that restrict the concentration of available oxygen. In this article, we describe a novel superhydrophobic singlet oxygen delivery device for the selective inactivation of bacterial biofilms. The device addresses the current limitations by: immobilizing photosensitizer molecules onto inert silica particles; embedding the photosensitizer-containing particles into the plastron (i.e. the fluid-free space within a superhydrophobic surface between the solid substrate and fluid layer); distributing the particles along an optically transparent substrate such that they can be uniformly illuminated; enabling the penetration of oxygen via the contiguous vapor space defined by the plastron; and stabilizing the superhydrophobic state while avoiding the direct contact of the sensitizer to biomaterials. In this way, singlet oxygen generated on the sensitizer-containing particles can diffuse across the plastron and kill bacteria even deep within the hypoxic periodontal pockets. For the first time, we demonstrate complete biofilm inactivation (>5 log killing) of Porphyromonas gingivalis, a bacterium implicated in periodontal disease using the superhydrophobic singlet oxygen delivery device. The biofilms were cultured on hydroxyapatite disks and exposed to active and control surfaces to assess the killing efficiency as monitored by colony counting and confocal microscopy. Two sensitizer particle types, a silicon phthalocyanine sol-gel and a chlorin e6 derivative covalently bound to fluorinated silica, were evaluated; the biofilm killing efficiency was found to correlate with the amount of singlet oxygen detected in separate trapping studies. Finally, we discuss the applications of such devices in the treatment of periodontitis.
Singlet oxygen is a potent agent for the selective killing of a wide range of pan class="Chemical">harmful cells; however, current delivery methods pose significant obstacles to its widespread use as a treatment agent. Limitations include the need for photosensitizer proximity to tissue because of the short (3.5 μs) lifetime of singlet oxygen in contact with water; the strong optical absorption of the photosensitizer, which limits the penetration depth; and hypoxic environments that restrict the concentration of available oxygen. In this article, we describe a novel superhydrophobic singlet oxygen delivery device for the selective inactivation of bacterial biofilms. The device addresses the current limitations by: immobilizing photosensitizer molecules onto inert silica particles; embedding the photosensitizer-containing particles into the plastron (i.e. the fluid-free space within a superhydrophobic surface between the solid substrate and fluid layer); distributing the particles along an optically transparent substrate such that they can be uniformly illuminated; enabling the penetration of oxygen via the contiguous vapor space defined by the plastron; and stabilizing the superhydrophobic state while avoiding the direct contact of the sensitizer to biomaterials. In this way, singlet oxygen generated on the sensitizer-containing particles can diffuse across the plastron and kill bacteria even deep within the hypoxic periodontal pockets. For the first time, we demonstrate complete biofilm inactivation (>5 log killing) of Porphyromonas gingivalis, a bacterium implicated in periodontal disease using the superhydrophobic singlet oxygen delivery device. The biofilms were cultured on hydroxyapatite disks and exposed to active and control surfaces to assess the killing efficiency as monitored by colony counting and confocal microscopy. Two sensitizer particle types, a silicon phthalocyanine sol-gel and a chlorin e6 derivative covalently bound to fluorinated silica, were evaluated; the biofilm killing efficiency was found to correlate with the amount of singlet oxygen detected in separate trapping studies. Finally, we discuss the applications of such devices in the treatment of periodontitis.
Entities:
Keywords:
biofilm eradication; dentistry; photodynamic therapy; singlet oxygen; superhydrophobic device