傳統牙齒漂白以過氧化氫藥劑為主，以產生過氧化物自由基來裂解色素體之雙鍵，以達到漂白作用。但由於過氧化氫本身的高酸性和氧化損傷，術後牙齒敏感性和軟組織刺激並不罕見。此外，由於有限的穿透深度，容易有牙齒顏色再回復或漂白不均勻的情況產生，因而更有效的牙齒漂白策略仍有待開發。

石墨氧化物是石墨烯生產的前體。氮摻雜氧化石墨烯量子點具有p-n型光化學二極體的特徵。當氧化還原由光能驅動時，會在SP2 軌道產生電子電洞對，將周圍物質進一步氧化還原，因此有被用來進行牙齒漂白的潛力。本實驗所使用的氮塗佈之氧化石墨烯量子點，修飾的胺基後能增加親水性及光催化效率，並可能與牙齒膠原產生較佳的親和性結合。，和光催化劑過程中的總反應表面積，實現可持續的功效。胺基氮塗佈之氧化石墨烯量子點(ANGOD)的極小奈米粒子，具有高滲透性，有機會將過氧化氫擴散到牙齒內層，進行更深層的牙齒漂白。

在試管內研究中，0.9 mM H2O2可以顯著溶解人工模擬四環黴素鐵/鈣/磷酸複合物。而0.05 mg/ml的 ANGOD加2 mM抗壞血酸在10分鍾光照下能產生0.6 mM H2O2。此外，依循ISO-10993-5的毒性驗證標準，我們亦發現ANGOD有很好的生物相容性。因此，以ANGOD和抗壞血酸結合光動力處理能可以發展成安全、為有效的牙齒漂白方法。

在體外牙齒漂白實驗則發現，四環素色素牙在以ANGOD和抗壞血酸結合加以陽光模擬器照射組所進行的光動力處理，僅7次照光漂白就能顯著改善四環素色素外染牙以及臨床四環素色素沉著的牙齒之染色。本研究顯示，將ANGOD和抗壞血酸結合光動力處理具有能被用來開發更先進、安全而持久的牙齒漂白染色系統的潛力。

Tooth whitening techniques have been developed using hydrogen peroxide containing agents as bleaching agents to generate radicals that cleave double-bond of the pigment molecules. However, due its low pH and oxidative damage, post-operative tooth sensitivity and soft tissues irritation are common side effects. Further, tooth discoloration may recur at focal or whole tooth after bleaching due to limited penetration depth. More effective tooth bleaching strategies remained to be developed.

Graphite oxide is a precursor of graphene production. Nitrogen-doped graphene oxide quantum dots have the character of p-n type photochemical diode. When the redox is driven by light energy, electron and hole are generated in the SP2 orbital and are capable of executing further redox reactions such as for tooth bleaching. Amonia-treated nitrogen-doped graphite oxide quantum dots (ANGOD) have been shown to improve the hydrophilicity as well as the photocatalytic capability and might also improve the affinity binding to tooth collagen. Such design would improve the deep penetration of the ANGOD and the well crystalized ANGOD is crucial for sustainable photodynamic bleaching process.

In the in vitro study, we observed that 0.9 mM H2O2 was able to significantly dissolved artificial stain complex, while 0.05 mg/ml ANGOD plus 2 mM ascorbic acid (AA) produced 0.6 mM H2O2 within 10 mins of irradiation. In addition, following the instruction of ISO-10993-5, we also showed that ANGODs is highly biocompatible. Thus, the combination of photodynamic treatment in the presence of ANGOD and AA could be potential for tooth bleaching. In the ex-vivo analysis, photodynamic treatment in the presence of ANGOD and AA showed a significant bleaching effect compared to other groups in both artificial tetracycline ex-stained tooth and tetracycline-pigmented tooth. In this study, we showed that the combination of photodynamic treatment in the presence of ANGOD and AA is potential for tooth bleaching.

References

1. Guazzo R, Gardin C, Bellin G, Sbricoli L, Ferroni L, Ludovichetti FS, Piattelli A, Antoniac I, Bressan E, Zavan B. Graphene-Based Nanomaterials for Tissue Engineering in the Dental Field. Nanomaterials 2018, 8(5): 349.
2. Su IH, Lee CF, Su YP, Wang LH. Evaluating a Cobalt-Tetraphenylporphyrin Complex, Functionalized with a Reduced Graphene Oxide Nanocomposite, for Improved Tooth Whitening. Journal of Esthetic and Restorative Dentistry 2016, 28(5): 321-329.
3. Achtyl JL, Unocic RR, Xu L, Cai Y, Raju M, Zhang W, Sacci RL, Vlassiouk IV, Fulvio PF, Ganesh P, Wesolowski DJ, Dai S, van Duin AC, Neurock M, Geiger FM. Aqueous Proton Transfer Across Single-Layer Graphene. Journal of Nature Communications 2015, 6: 6539.
4. Yeh TF, Teng CY, Chen SJ, Teng H. Nitrogen-Doped Graphene Oxide Quantum Dots as Photocatalysts for Overall Water-Splitting under Visible Light Illumination. Advanced Materials 2014, 26: 3297-3303.
5. Huang J, Hoc W, Wang X. Metal-Free Disinfection Effects Induced by Graphitic Carbon Nitride Polymers under Visible Light Illumination. Chemical Communications 2014, 50(33): 4338-4340.
6. Chen LC, Xiao YK, Ke NJ, Shih CY, Yeh TF, Lee YL, Teng H. Synergy between Quantum Confinement and Chemical Functionality of Graphene Dots Promotes Photocatalytic H2 Evolution. Journal of Materials Chemistry A 2018, 6(33): 18216-18224.
7. Goldberg M, Grootveld M, Lynch E. Undesirable and Adverse Effects of Tooth-Whitening Products: A Review. Clinical Oral Investigations 2010, 14(1): 1-10.
8. Bharti R, Wadhwani K. Spectrophotometric Evaluation of Peroxide Penetration into the Pulp Chamber from Whitening Strips and Gel: An in vitro Study. Journal of Conservative Dentistry 2013, 16(2): 131-134.
9. Kwon SR, Wertz PW. Review of the Mechanism of Tooth Whitening. Journal of Esthetic and Restorative Dentistry 2015, 27(5): 240-257.
10. Hanks C, Fat J, Wataha J, Corcoran J. Cytotoxicity and Dentin Permeability of Carbamide Peroxide and Hydrogen Peroxide Vital Bleaching Materials, in vitro. Journal of Dental Research 1993, 72(5): 931-938.
11. de Almeida LC, Costa CA, Riehl H, dos Santos PH, Sundfeld RH, Briso AL. Occurrence of Sensitivity During At-Home and In-Office Tooth Bleaching Therapies with or without Use of Light Sources. Acta odontológica Latinoamericana 2012, 25(1): 3-8.
12. Elfallah HM, Bertassoni LE, Charadram N, Rathsam C, Swain MV. Effect of Tooth Bleaching Agents on Protein Content and Mechanical Properties of Dental Enamel. Acta Biomaterialia 2015, 20: 120-128.
13. Redha O, Strange A, Maeva A, Sambrook R, Mordan N, McDonald A, Bozec L. Impact of Carbamide Peroxide Whitening Agent on Dentinal Collagen. Journal of Dental Research 2019, 98(4): 443-449.
14. Roderjan DA, Stanislawczuk R, Hebling J, de Souza Costa CA, Soares DG, Reis A, Loguercio AD. Histopathological Features of Dental Pulp Tissue from Bleached Mandibular Incisors. Materials Science and Engineering: B 2014, 4:178-185.
15. Costa CA, Riehl H, Kina JF, Sacono NT, Hebling J. Human Pulp Responses to In-Office Tooth Bleaching. Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology 2010, 109(4): e59-e64.
16. Skinner HC, Nalbandian J. Tetracyclines and Mineralized Tissues: Review and Perspectives. Yale Journal of Biology and Medicine 1975, 48: 377-397.
17. Blackwood RK. Tetracyclines. Encyclopedia of Chemical Technology 1963, 20: 325.
18. Albert A, Rees CW. Avidity of the Tetracyclines for the Cations of Metals. Nature 1956, 177: 433-434.
19. Ibsen KH, Urist MR. Competition between Oxytetracycline and Citrate for Binding Sites on Hydroxyapatite Crystals. Calcified Tissue International 1967, 1(3): 243-245.
20. Bowles WH. Protection against Minocycline Pigment Formation by Ascorbic Acid (Vitamin C). Journal of Esthetic Denstry 1998, 10(4): 182-186.
21. Düzgün G, Durmaz Akyol A. Effect of Natural Sunlight on Sleep Problems and Sleep Quality of the Elderly Staying in the Nursing Home. Holistic Nursing Practice 2017, 1(5): 295-302.
22. Carey CM. Tooth Whitening: What We Know Now. Journal of Evidence-Based Dental Practice 2014, 14: 70-76.
23. Alqahtani MQ. Tooth-Bleaching Procedures and Their Controversial Effects: A Literature Review. Saudi Dental Journal 2014, 26(2): 33-46.
24. Moghadam FV, Majidinia S, Chasteen J, Ghavamnasiri M. The Degree of Color Change, Rebound Effect and Sensitivity of Bleached Teeth Associated with At‐Home and Power Bleaching Techniques: A Randomized Clinical Trial. European Journal of Dentistry 2013, 7(4): 405-411.