Nanotechnology is currently driving the dental materials industry to substantial growth, thus reflecting on improvements in materials available for oral prevention and treatment. The present review discusses new developments in nanotechnology applied to dentistry, focusing on the use of nanomaterials for improving the quality of oral care, the perspectives of research in this arena, and discussions on safety concerns regarding the use of dental nanomaterials. Details are provided on the cutting-edge properties (morphological, antibacterial, mechanical, fluorescence, antitumoral, and remineralization and regeneration potential) of polymeric, metallic and inorganic nano-based materials, as well as their use as nanocluster fillers, in nanocomposites, mouthwashes, medicines, and biomimetic dental materials. Nanotoxicological aspects, clinical applications, and perspectives for these nanomaterials are also discussed. © 2015 Elsevier Ltd.3311621636Ghadimi, E., Regulated fracture in tooth enamel: a nanotechnological strategy from nature (2014) J. Biomech., 47, pp. 2444-2451Bhavikatti, S.K., Current applications of nanotechnology in dentistry: a review (2014) Gen. Dent., 62, pp. 72-77Bawa, R., Nanopharmaceuticals patenting issues and FDA regulatory challenges (2008) Sci. Tech. Lawyer, 5, pp. 1-6Potocnik, J., Commission recommendation of 18 October 2011 on the definition of nanomaterial (2011) Off. J. Eur. Union L, 275, pp. 38-40(2014) Considering Whether an FDA-Regulated Product Involves the Application of Nanotechnology, , US Department of Health and Human Services, Food and Drug Administration, Office of the CommissionerSauro, S., Therapeutic effects of novel resin bonding systems containing bioactive glasses on mineral-depleted areas within the bonded-dentine interface (2012) J. Mater. Sci. Mater. Med., 23, pp. 1521-1532Mantri, S.S., Mantri, S.P., The nano era in dentistry (2013) J. Nat. Sci. Biol. Med., 4, pp. 39-44Antunes, A.M.S., Trends in nanotechnology patents applied to the health sector (2012) Recent Pat. Nanotechnol., 6, pp. 29-43Luna, D.M.N., Andrade, C.A.S., Nanotechnology applied to dentistry (2011) Int. J. Dent., 10, pp. 161-168Uskoković, V., Bertassoni, L.E., Nanotechnology in dental sciences: moving towards a finer way of doing dentistry (2010) Materials, 3, pp. 1674-1691Kanaparthy, R., Kanaparthy, A., The changing face of dentistry: nanotechnology (2011) Int. J. Nanomed., 6, pp. 2799-2804Tomsia, A.P., Nanotechnology approaches for better dental implantas (2011) Int. J. Oral Maxillofac. Implants, 26, pp. 25-44Kovvuru, S.K., Nanotechnology: the emerging science in dentistry (2012) J. Orofac. Res., 2, pp. 33-36Kumar, P., Nanotechnological impact on future clinical dental prospects: an insight (2013) Eur. J. Gen. Dent., 2, pp. 86-87Mikkilineni, M., Nanodentistry: new buzz in dentistry (2013) Eur. J. Gen. Dent., 2, pp. 109-113Ozak, S.T., Ozkan, P., Nanotechnology and dentistry (2013) Eur. J. Dent., 7, pp. 145-151Lima, R., Silver nanoparticles: a brief review of cytotoxicity and genotoxicity of chemically and biogenically synthesized nanoparticles (2012) J. Appl. Toxicol., 32, pp. 867-879Marcato, P.D., Biogenic silver nanoparticles: antibacterial and cytotoxicity applied to textile fabrics (2012) J. Nano Res., 20, pp. 69-76Duran, N., Mechanistic aspects in the biogenic synthesis of extracellular metal nanoparticles by peptides, bacteria, fungi and plants (2011) Appl. Microbiol. Biotechnol., 90, pp. 1609-1624Besinis, A., The antibacterial effects of silver, titanium dioxide and silica dioxide nanoparticles compared to the dental disinfectant chlorhexidine on Streptococcus mutans using a suite of bioassays (2014) Nanotoxicology, 8, pp. 1-16Chaloupka, K., Nanosilver as a new generation of nanoproduct in biomedical applications (2010) Trends Biotechnol., 28, pp. 580-588Radzig, M.A., Antibacterial effects of silver nanoparticles on gram-negative bacteria: influence on the growth and biofilms formation, mechanisms of action (2013) Colloids Surf. B: Biointerfaces, 102, pp. 300-306Peulen, T.O., Wilkinson, K.J., Diffusion of nanoparticles in a biofilm (2011) Environ. Sci. Technol., 45, pp. 3367-3373Abu-Lail, N.I., Camesano, T.A., Role of lipopolysaccharides in the adhesion, retention, and transport of Escherichia coli JM109 (2003) Environ. Sci. Technol., 37, pp. 2173-2183García-Contreras, R., Perspectives for the use of silver nanoparticles in dental practice (2011) Int. Dent. J., 61, pp. 297-301Park, E.J., Silver nanoparticles induce cytotoxicity by a Trojan-horse type mechanism (2010) Toxicol. In Vitro, 24, pp. 872-878Yang, Z., A review of nanoparticle functionality and toxicity on the central nervous system (2010) J. R. Soc. Interface, 7, pp. S411-S422Schrand, A.M., Can silver nanoparticles be useful as potential biological labels? (2008) Nanotechnology, 19, p. 235104Hussain, S.M., In vitro toxicity of nanoparticles in BRL 3A rat liver cells (2005) Toxicol. In Vitro, 19, pp. 975-983Arora, S., Cellular responses induced by silver nanoparticles: in vitro studies (2008) Toxicol. Lett., 179, pp. 93-100Burd, A., A comparative study of the cytotoxicity of silver-based dressings in monolayer cell, tissue explant, and animal models (2007) Wound Repair Regen., 15, pp. 94-104Kumar, C.S.S.R., (2006) Nanomaterials: Toxicity, Health and Environmental Issues, , Wiley-VCH-Verlag, (Ed.)Hajipour, M.J., Antibacterial properties of nanoparticles (2012) Trends Biotechnol., 30, pp. 499-511Huh, A.J., Kwon, Y.J., 'Nanoantibiotics': a new paradigm for treating infectious diseases using nanomaterials in the antibiotics resistant era (2011) J. Control. Release, 156, pp. 128-145Huang, Z., Toxicological effect of ZnO nanoparticles based on bacteria (2008) Langmuir, 24, pp. 4140-4144Srakaew, V., Sodium-phosphorylated chitosan/zinc oxide complexes and evaluation of their cytocompatibility: an approach for periodontal dressing (2012) J. Biomater. Appl., 27, pp. 403-412Yuan, J.H., Determination, characterization and cytotoxicity on HELF cells of ZnO nanoparticles (2010) Colloids Surf. B: Biointerfaces, 76, pp. 145-150Yang, S.T., Cytotoxicity of zinc oxide nanoparticles: importance of microenvironment (2010) J. Nanosci. Nanotechnol., 10, pp. 8638-8645Wang, Y., A combined toxicity study of zinc oxide nanoparticles and vitamin C in food additives (2014) Nanoscale, 6, pp. 15333-15342Blecher, K., The growing role of nanotechnology in combating infectious disease (2011) Virulence, 2, pp. 395-401Adams, L.K., Comparative eco-toxicity of nanoscale TiO2, SiO2, and ZnO water suspensions (2006) Water Res., 40, pp. 3527-3532Garcia-Contreras, R., Induction of prostaglandin E2 production by TiO2 nanoparticles in human gingival fibroblast (2014) In Vivo, 28, pp. 217-222Garcia-Contreras, R., Effects of TiO2 nano glass ionomer cements against normal and cancer oral cells (2014) In Vivo, 28, pp. 895-907Wang, J.J., Cyto- and genotoxicity of ultrafine TiO2 particles in cultured human lymphoblastoid cells (2007) Mutat. Res., 628, pp. 99-106Allaker, R.P., The use of nanoparticles to control oral biofilm formation (2010) J. Dent. Res., 89, pp. 1175-1186Friedman, A.J., Antimicrobial and anti-inflammatory activity of chitosan-alginate nanoparticles: a targeted therapy for cutaneous pathogens (2013) J. Invest. Dermatol., 133, pp. 1231-1239Fernandes, J.C., In vitro screening for anti-microbial activity of chitosans and chitooligosaccharides, aiming at potential uses in functional textiles (2010) J. Microbiol. Biotechnol., 20, pp. 311-318Raafat, D., Insights into the mode of action of chitosan as an antibacterial compound (2008) Appl. Environ. Microbiol., 74, pp. 3764-3773Kong, M., Antibacterial mechanism of chitosan microspheres in a solid dispersing system against E. coli (2008) Colloids Surf. B: Biointerfaces, 65, pp. 197-202Beyth, N., Long-term antibacterial surface properties of composite resin incorporating polyethyleneimine nanoparticles (2010) Quintessence Int., 41, pp. 827-835Beyth, N., Antibacterial activity of dental cements containing quaternary ammonium polyethylenimine nanoparticles (2012) J. Nanomater., 2012, pp. 814763-814766Zhang, K., Effect of water-ageing on dentine bond strength and anti-biofilm activity of bonding agent containing new monomer dimethylaminododecyl methacrylate (2013) J. Dent., 41, pp. 504-513Gong, S.-Q., Synthesis of antimicrobial silsesquioxane-silica hybrids by hydrolytic co-condensation of alkoxysilanes (2014) Polym. Chem., 5, pp. 454-462Gong, S.Q., In vitro evaluation of antibacterial effect of AH Plus incorporated with quaternary ammonium epoxy silicate against Enterococcus faecalis (2014) J. Endod., 40, pp. 1611-1615Zhuo Sun, X., The antimicrobial activities of a series of bis-quaternary ammonium compounds (2011) Chinese Chem. Lett., 22, pp. 887-890Melo, M.A., Nanotechnology-based restorative materials for dental caries management (2013) Trends Biotechnol., 31, pp. 459-467De Jong, W.H., Borm, P.J., Drug delivery and nanoparticles:applications and hazards (2008) Int. J. Nanomed., 3, pp. 133-149Brannon-Peppas, L., Blanchette, J.O., Nanoparticle and targeted systems for cancer therapy (2012) Adv. Drug Deliv. Rev., 64, pp. 206-212Endo, K., Tumor-targeted chemotherapy with the nanopolymer-based drug NC-6004 for oral squamous cell carcinoma (2013) Cancer Sci., 104, pp. 369-374Holpuch, A.S., Nanoparticles for local drug delivery to the oral mucosa: proof of principle studies (2010) Pharm. Res., 27, pp. 1224-1236Pinon-Segundo, E., Preparation and characterization of triclosan nanoparticles for periodontal treatment (2005) Int. J. Pharm., 294, pp. 217-232Shrestha, A., Nanoparticulates for antibiofilm treatment and effect of aging on its antibacterial activity (2010) J. Endod., 36, pp. 1030-1035Bahram, M., Synthesis of gold nanoparticles using pH-sensitive hydrogel and its application for colorimetric determination of acetaminophen, ascorbic acid and folic acid (2014) Colloids Surf. A, 441, pp. 517-524Saito, N., Carbon nanotubes: biomaterial applications (2009) Chem. Soc. Rev., 38, pp. 1897-1903Mao, H.Y., Graphene: promises, facts, opportunities, and challenges in nanomedicine (2013) Chem. Rev., 8, pp. 3407-3424Akasaka, T., Modification of the dentin surface by using carbon nanotubes (2009) Biomed. Mater. Eng., 19, pp. 179-185Zhang, H., Antibacterial activity of endodontic sealers by modified direct contact test against Enterococcus faecalis (2009) J. Endod., 35, pp. 1051-1055Wagner, M.K., Use of quantum dots in the development of assays for cancer biomarkers (2010) Anal. Bioanal. Chem., 397, pp. 3213-3224Cai, W., Applications of gold nanoparticles in cancer nanotechnology (2008) Nanotechnol. Sci. Appl., 2008, pp. 17-32Jain, S., Gold nanoparticles as novel agents for cancer therapy (2012) Br. J. Radiol., 85, pp. 101-113Van Landuyt, K.L., Nanoparticle release from dental composites (2014) Acta Biomater., 10, pp. 365-374Bowen, R.L., Dental filling materials comprising of vinyl-silane resin-based composites fused silica and binder consisting of the reaction product of bis phenol and glycidyl methacrylate, US 3066112Curtis, A.R., Water uptake and strength characteristics of a nanofilled resin-based composite (2008) J. Dent., 36, pp. 186-193Kim, Y., Effect of nano-carbonate apatite to prevent re-stain after dental bleaching in vitro (2011) J. Dent., 39, pp. 636-642Ernst, C.P., Two-year clinical performance of a nanofiller vs a fine-particle hybrid resin composite (2006) Clin. Oral Investig., 10, pp. 119-125Deng, D., Synthesis of newbantibacterial quaternary ammonium monomer for incorporation into CaP nanocomposite (2013) Dent. Mater., 29, pp. 859-870Melo, M.A., Novel dental adhesive containing antibacterial agents and calcium phosphate nanoparticles (2013) J. Biomed. Mater. Res. Part B Appl. Biomater., 10, pp. 620-629Zhang, K., Effect of quaternary ammonium and silver nanoparticle-containing adhesives on dentin bond strength and dental plaque microcosm biofilms (2012) Dent. Mater., 28, pp. 842-852Feitosa, S.A., Doxycycline-encapsulated nanotube-modified dentin adhesives (2014) J. Dent. Res., 93, pp. 1270-1276Turagan, N., Mudrakota, D.P., Effect of micro-additions of carbon nanotubes to polymethylmethacrylate on reduction in polymerization shrinkage (2013) J. Prosthodont., 22, pp. 105-111Moraes, R.R., Control of polymerization shrinkage and stress in nanogel-modified monomer and composite materials (2011) Dent. Mater., 27, pp. 509-519Moraes, R.R., Improved dental adhesive formulations based on reactive nanogel additives (2012) J. Dent. Res., 91, pp. 179-184Dailing, E.A., Construction of monomer-free, highly crosslinked, water-compatible polymers (2014) J. Dent. Res., 93, pp. 1326-1331Azami, M., Synthesis and solubility of calcium fluoride/hydroxyl-fluorapatite nanocrystals for dental applications (2011) Ceram. Int., 37, pp. 2007-2014Xu, H.H., Nanocomposite containing amorphous calcium phosphate nanoparticles for caries inhibition (2011) Dent. Mater., 27, pp. 762-769Chow, L.C., Ada Foundation, , Consisting of filler of nano particles of dicalcium phosphate anhydrous having particle size of 50nm to 200nm, strengthener of SiC curable resin including bisphenol glycidyl methacrylate (Bis-GMA), US 20090093566 A1De-Deus, G., Optimal cytocompatibility of a bioceramic nanoparticulate cement in primary human mesenchymal cells (2009) J. Endod., 35, pp. 1387-1390Yuan, Z., Effect of bioaggregate on mineral-associated gene expression in osteoblast cells (2010) J. Endod., 36, pp. 1145-1148Min, J., The addition of nano-sized hydroxyapatite to a sports drink to inhibit dental erosion - in vitro study using bovine enamel (2011) J. Dent., 39, pp. 629-635Srinivasan, S., Biocompatible alginate/nano bioactive glass ceramic composite scaffolds for periodontal tissue regeneration (2012) Carbohydr. Polym., 87, pp. 274-283Lainovic, T., Nanotechnology in dentistry - current state and future perspectives (2012) Serbian Dent. J., 59, pp. 44-47Abrishamchian, A., Preparation and characterization of multi-walled carbon nanotube/hydroxyapatite nanocomposite film dip coated on Ti-6Al-4V by sol-gel method for biomedical applications: an in vitro study (2013) Mater. Sci. Eng. C: Mater. Biol. Appl., 33, pp. 2002-2010Lee, H.H., Biomedical nanocomposites of poly(lactic acid) and calcium phosphate hybridized with modified carbon nanotubes for hard tissue implants (2011) J. Biomed. Mater. Res. B: Appl. Biomater., 98, pp. 246-254Yoshida, Y., Self-assembled nano-layering at the adhesive interface (2012) J. Dent. Res., 91, pp. 376-381Yoshihara, K., Nanolayering of phosphoric acid ester monomer on enamel and dentin (2011) Acta Biomater., 7, pp. 3187-3195Niu, L.N., Biomimetic remineralization of dentin (2014) Dent. Mater., 30, pp. 77-96Fioretti, F., Nanostructured assemblies for dental applications (2010) ACS Nano, 4, pp. 3277-3287Fioretti, F., Nano-odontology: nanostructured assemblies for endodontic regeneration (2011) J. Biomed. Nanotechnol., 7, pp. 471-475Besinis, A., Remineralization potential of fully demineralized dentin infiltrated with silica and hydroxyapatite nanoparticles (2014) Dent. Mater., 30, pp. 249-262Sauro, S., Influence of phosphoproteins' biomimetic analogs on remineralization of mineral-depleted resin-dentin interfaces created with ion-releasing resin-based systems (2015) Dent. Mater., 31, pp. 759-777Hannig, C., Hannig, M., Natural enamel wear - a physiological source of hydroxyapatite nanoparticles for biofilm management and tooth repair? (2010) Med. Hypotheses, 74, pp. 670-672Kim, J.K., Differentiating dental pulp cells via RGD-dendrimer conjugates (2010) J. Dent. Res., 89, pp. 1433-1438Chen, L., Regeneration of biomimetic hydroxyapatite on etched human enamel by anionic PAMAM template in vitro (2013) Arch. Oral Biol., 58, pp. 975-980Wu, D., Hydroxyapatite-anchored dendrimer for in situ remineralization of human tooth enamel (2013) Biomaterials, 34, pp. 5036-5047Li, J., Bioinspired intrafibrillar mineralization of human dentine by PAMAM dendrimer (2013) Biomaterials, 34, pp. 6738-6747Vallittu, P., Dental and medical polymer composites and compositions, , CA 2437622 A1Kangasniemi, L., Dental or medical device, , WO 2003030837 A1Zech, J., Lechner, G., 3M ESPE AG. Hardenable mass with silane dendrimers, , US 20026335413 B1Dodiuk-Kenig, H., Premier Dental Products Company Dental compostions based on nanofiber reinforcement, , WO 2007024652Brandenburg, C.J., Cohen, G.M., Pont, D., Tri (Meth) acrylate-based dendrimers as base monomers for materials leading to improved dental composites and dental composites made therefrom, WO 2006031970A1De Fúcio, S.B., Biomechanical degradation of the nano-filled resin-modified glass-ionomer surface (2012) Am. J. Dent., 25, pp. 315-320Yen, A.H., Yelick, P.C., Dental tissue regeneration- a mini-review (2011) Gerontology, 57, pp. 85-94Xavier, J.R., Promises for improved dental tissue regeneration (2015) Nanotechnology in Endodontics, pp. 5-22. , Springer, A. Kishen (Ed.)Moghadas, L., Shahmoradi, M., The University Of British Columbia Composition and method for irrigation of dental root canal, , AU 2012100480A4Corral, J.S.M., Consejo Superior de Investigaciones Cientificas (CSIC). Nanostructured calcium-silver phosphate composite powder, method for obtaining same, and bactericidal and fungicidal uses thereof, EP 2380687 A1Bobeshko, M.N., Modified adhesive composition for blade denture fixation, , RU 20112444349 C2Jin, G., Synergistic effects of dual Zn/Ag ion implantation in osteogenic activity and antibacterial ability of titanium (2014) Biomaterials, 35, pp. 7699-76713Espinosa-Cristóbal, L.F., Adherence inhibition of Streptococcus mutans on dental enamel surface using silver nanoparticles (2013) Mater. Sci. Eng. C: Mater. Biol. Appl., 33, pp. 2197-2202Bawaskar, M., A new report on mycosynthesis of silver nanoparticles by Fusarium culmorum (2010) Curr. Nanosci., 6, pp. 376-380Huang, L., Synergistic combination of chitosan acetate with nanoparticle silver as a topical antimicrobial: efficacy against bacterial burn infections (2011) Antimicrob. Agents Chemother., 55, pp. 3432-3438Fayaz, A.M., Biogenic synthesis of silver nanoparticles and their synergistic effect with antibiotics: a study against gram-positive and gram-negative bacteria (2010) Nanomedicine, 6, pp. 103-109Melo, M.A., Novel dental adhesives containing nanoparticles of silver and amorphous calcium phosphate (2013) Dent. Mater., 29, pp. 199-210Cheng, L., Antibacterial amorphous calcium phosphate nanocomposites with a quaternary ammonium dimethacrylate and silver nanoparticles (2012) Dent. Mater., 28, pp. 561-572Santos, V.E., A new 'silver-bullet' to treat caries in children - nano silver fluoride: a randomised clinical trial (2014) J. Dent., 42, pp. 945-951Memarzadeh, K., Nanoparticulate zinc oxide as a coating material for orthopedic and dental implants (2015) J. Biomed. Mater. Res. Part A, 103, pp. 981-989Toledano, M., A Zn-doped etch-and-rinse adhesive may improve the mechanical properties and the integrity at the bonded-dentin interface (2013) Dent. Mater., 29, pp. e142-e152Osorio, R., Zinc incorporation improves biological activity of beta-tricalcium silicate resin-based cement (2014) J. Endod., 40, pp. 1840-1845Kasraei, S., Antibacterial properties of composite resins incorporating silver and zinc oxide nanoparticles on Streptococcus mutans and Lactobacillus (2014) Restor. Dent. Endod., 39, pp. 109-114Vargas-Reus, M.A., Antimicrobial activity of nanoparticulate metal oxides against peri-implantitis pathogens (2012) Int. J. Antimicrob. Agents, 40, pp. 135-139Guerreiro-Tanomaru, J.M., Effect of zirconium oxide and zinc oxide nanoparticles on physicochemical properties and antibiofilm activity of a calcium silicate-based material (2014) Sci. World J., 2014, p. 975213Poosti, M., Shear bond strength and antibacterial effects of orthodontic composite containing TiO2 nanoparticles (2013) Eur. J. Orthod., 35, pp. 676-679Liu, W., Synthesis of TiO2 nanotubes with ZnO nanoparticles to achieve antibacterial properties and stem cell compatibility (2014) Nanoscale, 6, pp. 9050-9062Martin, J., Effectiveness of 6% hydrogen peroxide concentration for tooth bleaching - a double-blind, randomized clinical trial (2015) J. Dent., 43, pp. 965-972Targino, A.G.R., An innovative approach to treating dental decay in children. A new anti-caries agent (2014) J. Mater. Sci. Mater. Med., 25, pp. 2041-2047Kim, S.H., Immobilization of BMP-2 on a nano-hydroxyapatite-coated titanium surface using a chitosan calcium chelating agent (2013) Int. J. Artif. Organs, 36, pp. 506-517Beytha, N., Polyethyleneimine nanoparticles incorporated into resin composite cause cell death and trigger biofilm stress in vivo (2010) Proc. Natl. Acad. Sci. U.S.A., 107, pp. 22038-22043