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Title: Upconversion Nanoparticle-Based Photodynamic Inactivation of Viruses
Keywords: Upconversion, Nanoparticle, Virus, Photosensitizer, Photodynamic therapy, Photodynamic inactivation
Issue Date: 18-Aug-2011
Citation: LIM MENG EARN (2011-08-18). Upconversion Nanoparticle-Based Photodynamic Inactivation of Viruses. ScholarBank@NUS Repository.
Abstract: Current virus inactivation strategies are working toward targeted inhibition of viral replication machinery by antiviral drugs. In addition, vaccination is another widely used strategy. However, the genetic and serological heterogeneities of viruses hamper the development of effective vaccines or antiviral drugs that work against all viruses of different serotypes and strains. Meanwhile, viruses that mutate rapidly will render the vaccines or antiviral drugs to be ineffective. An alternative strategy in virus inactivation can be achieved through a light-based approach called photodynamic therapy (PDT). This approach requires the excitation of light-sensitive materials called photosensitizers to produce reactive oxygen species which mediate the inactivation of viruses. PDT results in the direct inactivation of viruses without depending on the host-virus responses. Although photodynamic effect has been demonstrated against viruses, it has been slow in gaining acceptance, mainly because of the hydrophobicity of photosentizers and current light sources used, which have limited tissue penetration ability. Here, we report a novel upconversion nanoparticle-based PDT to photodynamically inactivate viruses. In this strategy, photosensitizers are loaded onto the near-infrared (NIR)-to-visible upconversion nanoparticles (UCNs). When the nanoparticles are irradiated with NIR light at 980 nm, the UCNs emit visible light which is being absorbed by the photosensitizers. The excited photosensitizers then convert nearby molecular oxygen to toxic singlet oxygen species, which mediate viral inactivation. The UCNs act as nanocarriers of the highly hydrophobic photosensitizers as well as nanotransducers that convert NIR light to visible emissions necessary for the excitation of photosensitizers. The use of NIR light introduces several advantages such as high light penetration depth in vivo and minimal photodamage to cells and tissues. The synthesized UCNs emit strong upconversion fluorescence by producing visible emissions in the green and red regions with peaks at 545 nm and 658 nm respectively when the UCNs were being irradiated with NIR light at 980 nm. ZnPc was used as the photosensitizer in this work due to its high absorption coefficient and quantum yields. Singlet oxygen is consistently being released from the UCNs over time. Using both PEI-coated and mesoporous silica-coated UCNs, we observed a significant decrease in virus titers when the Dengue viruses were irradiated in the presence of UCNs, demonstrating the feasibility of UCN-based system for photodynamic inactivation of viruses. In another development, NIR light was shown to penetrate mouse tissues and photodynamic inactivation of viruses beneath the skin tissues was achieved. The findings from this work demonstrate the feasibility of UCN-based PDT to photodynamically inactivate viruses with advantages over current PDT technique. Moreover, it further realizes the potential of utilizing this strategy in treating localized viral infections, especially thick lesions and warts of cutaneous diseases.
Appears in Collections:Master's Theses (Open)

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