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Anti-Biofilm Property of Bioactive Upconversion Nanocomposites

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Anti-Biofilm Property of Bioactive Upconversion Nanocomposites ( anti-biofilm-property-bioactive-upconversion-nanocomposites )

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Molecules 2019, 24, 2692 10 of 17 periodontitis treatment. We combine the upconversion luminescent material and the photosensitizer so that the near-infrared light with high tissue penetration depth can be utilized. More importantly, traditional aPDT had a minimal effect on the viability of microorganisms organized in a bacterial biofilm, which was probably due to the hydrophobic nature of the most photosensitizer molecules, leading to the reduced penetration of the photosensitizer into the biofilm matrix. The present study developed a silane coating as the shell of the UCNPs and embedded Ce6 inside the thin layer. This design would improve the hydrophilicity of the nanoparticles, and thus overcome the drainage of gingival crevicular fluid and high saliva fluid turnover [24]. Furthermore, the energy transfer would be more efficient for aPDT triggering due to the existence of Ce6 in the hydrophilic thin layer of the NPs. Therefore, this is a new exploration for the treatment of oral periodontitis, which is of great significance. There are two possible aPDT mechanisms which can be described as follows: The triplet state photosensitizer Ce6 either can undergo a type I reaction, or a type II reaction. Type I: excited triplet Ce6 reacts directly with the macromolecule (protein, nucleic acid, lipids, etc.), generating free radicals or free radical ions by electron transfer, and further react with oxygen molecules, forming highly reactive oxides such as hydroxyl radicals, peroxides, etc. Type II: triplet photosensitizer Ce6 react with surrounding ground state oxygen molecules, generating singlet oxygen, which has ultrahigh cytotoxicity by oxidation and peroxidation of the cellular structure, microbial attack, destruction of the cell wall, and membrane system damage, thus affecting microbial metabolism and leading to cell death [33,34]. In this work, NaYF4@Ce6@silane nanocrystals release singlet oxygen through a type II reaction, which can penetrate into plaque and subsequently kill bacteria. Note that the nanosized material can enter the microorganisms by endocytosis which has been proven in previous studies [35–37]. In the present study, the high permeability of silane modified UCNPs are responsible for the efficient reactive oxygen generation and PDT effect. Regarding the periodontitis treatment, aPDT that produces ROS possibly would not exacerbate the inflammatory response due to the following reasons: First, the role of PDT in inflammation is a complex process. Indeed, in tumor therapy, PDT could produce a strong inflammatory response of infiltration with neutrophils, mast cells, lymphocytes, monocytes, and macrophages [38]. However, PDT could also increase the stability of interleukin 10 (IL-10) RNA and/or increase the transcription efficiency of IL-10, which is an anti-inflammatory cytokine that inhibited cell-mediated immune responses [39]. Gollnick et al [40] reported that PDT could change the activity of a gene promoter and increase the expression level of IL-10. Therefore, these two processes may co-exist in the PDT therapy. Second, in general, 1O2 diffusion distance is only about 100 nm, and the half-life is <0.04 μs [41], the photosensitizer should be precisely delivered to the area of periodontal disease. Hence, the distance of 1O2 diffusion to the bacterial cells is of significant importance for the aPDT activity. Henderson et al. proposed that the 1O2-induced photodamage from porphyrin activation is usually localized to within 0.1 μm of its site of release [42]. Therefore, when the sterilization process is completed, the energy will disappear and the inflammation promotion effect on normal tissues is limited. These should be the main reasons for the efficient antibacterial properties, but without obvious inflammation. Alternatively, it is a promising approach to incorporation of anti-inflammatory agents (such as ceria, etc.) into the design of nanoparticles for aPDT application to reduce the potential risks in the future [43]. Considering the complicated oral structure and infectious area is always in deep tissue, these 980 nm laser excited UCNPs with large penetration depth are the most suitable photosensitizer carriers and energy transfer donors for antibacterial application. In addition, the Ce6 molecules are located on the surface of the UCNPs within very close distance because of the very thin silane-modified layer, forming the very close excitation distance. Therefore, besides the enhanced upconversion red light emission from NaYF4 UCNPs, efficient 1O2 production can be obtained for the antibacterial action against periodontal pathogens.

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