Magnetic-Responsive Photosensitizer Nanoplatform for Optimized Inactivation of Dental Caries-Related Biofilms: Technology Development and Proof of Principle.

Conventional antibiotic therapies for biofilm-trigged oral diseases are becoming less efficient due to the emergence of antibiotic-resistant bacterial strains. Antimicrobial photodynamic therapy (aPDT) is hampered by restricted access to bacterial communities embedded within the dense extracellular matrix of mature biofilms. Herein, a versatile photosensitizer nanoplatform (named MagTBO) was designed to overcome this obstacle by integrating toluidine-blue ortho (TBO) photosensitizer and superparamagnetic iron oxide nanoparticles (SPIONs) via a microemulsion method. In this study, we reported the preparation, characterization, and application of MagTBO for aPDT. In the presence of an external magnetic field, the MagTBO microemulsion can be driven and penetrate deep sites inside the biofilms, resulting in an improved photodynamic disinfection effect compared to using TBO alone. Besides, the obtained MagTBO microemulsions revealed excellent water solubility and stability over time, enhanced the aPDT performance against S. mutans and saliva-derived multispecies biofilms, and improved the TBO's biocompatibility. Such results demonstrate a proof-of-principle for using microemulsion as a delivery vehicle and magnetic field as a navigation approach to intensify the antibacterial action of currently available photosensitizers, leading to efficient modulation of pathogenic oral biofilms.

[1]  Won-Ho Kang,et al.  Safety verification for polysorbate 20, pharmaceutical excipient for intramuscular administration, in Sprague-Dawley rats and New Zealand White rabbits , 2021, PloS one.

[2]  M. Weir,et al.  Bifunctional Composites for Biofilms Modulation on Cervical Restorations , 2021, Journal of dental research.

[3]  F. Martinho,et al.  Advancing Photodynamic Therapy for Endodontic Disinfection with Nanoparticles: Present Evidence and Upcoming Approaches , 2021, Applied Sciences.

[4]  A. Radaic,et al.  The oralome and its dysbiosis: New insights into oral microbiome-host interactions , 2021, Computational and structural biotechnology journal.

[5]  P. G. de Barros Silva,et al.  The Impact of Photosensitizers Selection on Bactericidal Efficacy Of PDT against Cariogenic Biofilms: A Systematic Review and Meta-Analysis. , 2020, Photodiagnosis and photodynamic therapy.

[6]  F. Martinho,et al.  Light Energy Dose and Photosensitizer Concentration Are Determinants of Effective Photo-Killing against Caries-Related Biofilms , 2020, International journal of molecular sciences.

[7]  A. L. Ruela,et al.  ANTIMICROBIAL PHOTODYNAMIC THERAPY IN DENTISTRY USING AN OIL-IN-WATER MICROEMULSION WITH CURCUMIN AS A MOUTHWASH. , 2020, Photodiagnosis and photodynamic therapy.

[8]  D. Arola,et al.  Bioactive Low-Shrinkage-Stress Nanocomposite Suppresses S. mutans Biofilm and Preserves Tooth Dentin Hardness. , 2020, Acta biomaterialia.

[9]  T. Oates,et al.  Novel CaF2 Nanocomposites with Antibacterial Function and Fluoride and Calcium Ion Release to Inhibit Oral Biofilm and Protect Teeth , 2020, Journal of functional biomaterials.

[10]  M. Weir,et al.  Emerging Contact-Killing Antibacterial Strategies for Developing Anti-Biofilm Dental Polymeric Restorative Materials , 2020, Bioengineering.

[11]  F. Martinho,et al.  Prospects on Nano-Based Platforms for Antimicrobial Photodynamic Therapy Against Oral Biofilms. , 2020, Photobiomodulation, photomedicine, and laser surgery.

[12]  J. Camacho,et al.  A Unified View on Magnetic Nanoparticle Separation Under Magnetophoresis. , 2020, Langmuir : the ACS journal of surfaces and colloids.

[13]  M. Weir,et al.  Concentration dependence of quaternary ammonium monomer on the design of high-performance bioactive composite for root caries restorations. , 2020, Dental materials : official publication of the Academy of Dental Materials.

[14]  Jirun Sun,et al.  Novel low-shrinkage-stress nanocomposite with remineralization and antibacterial abilities to protect marginal enamel under biofilm. , 2020, Journal of dentistry.

[15]  C. Nunes,et al.  Innovative Strategies Toward the Disassembly of the EPS Matrix in Bacterial Biofilms , 2020, Frontiers in Microbiology.

[16]  Musa Hassan Muhammad,et al.  Beyond Risk: Bacterial Biofilms and Their Regulating Approaches , 2020, Frontiers in Microbiology.

[17]  N. Al-Rawi,et al.  Magnetism in drug delivery: The marvels of iron oxides and substituted ferrites nanoparticles , 2020, Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society.

[18]  S. Low,et al.  Sedimentation kinetics of magnetic nanoparticle clusters: Iron oxide nanospheres vs nanorods. , 2020, Langmuir : the ACS journal of surfaces and colloids.

[19]  D. Raoult,et al.  Bacterial culture through selective and non-selective conditions: the evolution of culture media in clinical microbiology , 2019, New microbes and new infections.

[20]  T. Gonçalves,et al.  An Insight into Advanced Approaches for Photosensitizer Optimization in Endodontics—A Critical Review , 2019, Journal of functional biomaterials.

[21]  F. Tay,et al.  Advancing antimicrobial strategies for managing oral biofilm infections , 2019, International Journal of Oral Science.

[22]  Biao Dong,et al.  Nanoparticles having amphiphilic silane containing Chlorin e6 with strong anti-biofilm activity against periodontitis-related pathogens. , 2019, Journal of dentistry.

[23]  Y. Ruiz,et al.  Stability and antimicrobial activity of eucalyptus essential oil emulsions , 2018, Food science and technology international = Ciencia y tecnologia de los alimentos internacional.

[24]  G. Sulaiman,et al.  Biosynthesis, characterization of magnetic iron oxide nanoparticles and evaluations of the cytotoxicity and DNA damage of human breast carcinoma cell lines , 2018, Artificial cells, nanomedicine, and biotechnology.

[25]  Yalin Zhang,et al.  Microemulsion formulation of a new biopesticide to control the diamondback moth (Lepidoptera: Plutellidae) , 2018, Scientific Reports.

[26]  Chi-Hsien Liu,et al.  Increased anti-biofilm efficacy of toluidine blue on Staphylococcus species after nano-encapsulation. , 2018, Photodiagnosis and photodynamic therapy.

[27]  Elizabeth J. Osterlund,et al.  BCL-2 family proteins: changing partners in the dance towards death. , 2018 .

[28]  W. Bowen,et al.  Oral Biofilms: Pathogens, Matrix, and Polymicrobial Interactions in Microenvironments. , 2017, Trends in microbiology.

[29]  S. Wettig,et al.  Microemulsion utility in pharmaceuticals: Implications for multi-drug delivery. , 2017, International journal of pharmaceutics.

[30]  F. Camacho-Alonso,et al.  Bactericidal Efficacy of Photodynamic Therapy and Chitosan in Root Canals Experimentally Infected with Enterococcus faecalis: An In Vitro Study. , 2017, Photomedicine and laser surgery.

[31]  Hongwei Song,et al.  Amphiphilic Silane Modified Multifunctional Nanoparticles for Magnetically Targeted Photodynamic Therapy. , 2017, ACS applied materials & interfaces.

[32]  T. Tsai,et al.  Assessment of Photodynamic Inactivation against Periodontal Bacteria Mediated by a Chitosan Hydrogel in a 3D Gingival Model , 2016, International journal of molecular sciences.

[33]  Mihail I Mitov,et al.  Targeted iron oxide nanoparticles for the enhancement of radiation therapy. , 2016, Biomaterials.

[34]  A. F. Ferreira Zandoná,et al.  Photo Inactivation of Streptococcus mutans Biofilm by Violet-Blue light , 2016, Current Microbiology.

[35]  Mette Burmølle,et al.  Studying Bacterial Multispecies Biofilms: Where to Start? , 2016, Trends in microbiology.

[36]  Lily Yang,et al.  Magnetic Nanoparticle Facilitated Drug Delivery for Cancer Therapy with Targeted and Image‐Guided Approaches , 2016, Advanced functional materials.

[37]  Chi-Hsien Liu,et al.  Enhancement of photodynamic inactivation against Pseudomonas aeruginosa by a nano-carrier approach. , 2016, Colloids and surfaces. B, Biointerfaces.

[38]  Asad U. Khan,et al.  Antibiofilm action of a toluidine blue O-silver nanoparticle conjugate on Streptococcus mutans: a mechanism of type I photodynamic therapy , 2016, Biofouling.

[39]  Harald Unterweger,et al.  Magnetic nanoparticle-based drug delivery for cancer therapy. , 2015, Biochemical and biophysical research communications.

[40]  L. Rodrigues,et al.  Photodynamic antimicrobial chemotherapy and ultraconservative caries removal linked for management of deep caries lesions. , 2015, Photodiagnosis and photodynamic therapy.

[41]  Kuldeep Singh,et al.  Aprepitant loaded solid preconcentrated microemulsion for enhanced bioavailability: A comparison with micronized Aprepitant. , 2015, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[42]  R. Gomez,et al.  Antimicrobial effect of photodynamic therapy in carious lesions in vivo, using culture and real-time PCR methods. , 2015, Photodiagnosis and photodynamic therapy.

[43]  S. Anne Photodynamic antimicrobial chemotherapy as a strategy for dental caries: building a more conservative therapy in restorative dentistry. , 2014 .

[44]  P. Pithayanukul,et al.  Microemulsion System for Topical Delivery of Thai Mango Seed Kernel Extract: Development, Physicochemical Characterisation and Ex Vivo Skin Permeation Studies , 2014, Molecules.

[45]  P. Breen,et al.  Drug dissolution: significance of physicochemical properties and physiological conditions. , 2013, Drug discovery today.

[46]  Michael R Hamblin,et al.  Antimicrobial strategies centered around reactive oxygen species--bactericidal antibiotics, photodynamic therapy, and beyond. , 2013, FEMS microbiology reviews.

[47]  X. Lou,et al.  Controlling silica coating thickness on TiO2 nanoparticles for effective photodynamic therapy. , 2013, Colloids and surfaces. B, Biointerfaces.

[48]  Michael R Hamblin,et al.  Photodynamic inactivation of biofilm: taking a lightly colored approach to stubborn infection , 2013, Expert review of anti-infective therapy.

[49]  J. Castell,et al.  Dichloro-dihydro-fluorescein diacetate (DCFH-DA) assay: a quantitative method for oxidative stress assessment of nanoparticle-treated cells. , 2013, Toxicology in vitro : an international journal published in association with BIBRA.

[50]  T. Mang,et al.  Photodynamic therapy as an alternative treatment for disinfection of bacteria in oral biofilms , 2012, Lasers in surgery and medicine.

[51]  S. Gibaud,et al.  Microemulsions for oral administration and their therapeutic applications , 2012, Expert opinion on drug delivery.

[52]  A. Tedesco,et al.  A delivery system to avoid self-aggregation and to improve in vitro and in vivo skin delivery of a phthalocyanine derivative used in the photodynamic therapy. , 2011, Journal of controlled release : official journal of the Controlled Release Society.

[53]  M. Simionato,et al.  Clinical use of photodynamic antimicrobial chemotherapy for the treatment of deep carious lesions. , 2011, Journal of biomedical optics.

[54]  Lutz Trahms,et al.  Cancer therapy with drug loaded magnetic nanoparticles—magnetic drug targeting , 2011 .

[55]  Lei Shen,et al.  Tween surfactants: Adsorption, self-organization, and protein resistance , 2011 .

[56]  T. Beikler,et al.  Control of oral biofilms. , 2011, Periodontology 2000.

[57]  Shan Ren,et al.  New perspectives on lipid and surfactant based drug delivery systems for oral delivery of poorly soluble drugs , 2010, The Journal of pharmacy and pharmacology.

[58]  H. Flemming,et al.  The biofilm matrix , 2010, Nature Reviews Microbiology.

[59]  A. Badawi,et al.  Preparation and Evaluation of Microemulsion Systems Containing Salicylic Acid , 2009, AAPS PharmSciTech.

[60]  Yin-Kai Chen,et al.  The promotion of human mesenchymal stem cell proliferation by superparamagnetic iron oxide nanoparticles. , 2009, Biomaterials.

[61]  Michael T. Wilson,et al.  Gold Nanoparticles Enhance the Toluidine Blue-Induced Lethal Photosensitisation of Staphylococcus aureus , 2008 .

[62]  F Bakkali,et al.  Biological effects of essential oils--a review. , 2008, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[63]  Yu Zhang,et al.  Intrinsic peroxidase-like activity of ferromagnetic nanoparticles. , 2007, Nature nanotechnology.

[64]  Michael R Hamblin,et al.  Photodynamic therapy: a new antimicrobial approach to infectious disease? , 2004, Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology.

[65]  G. Andrei,et al.  Iron chelators inhibit the growth and induce the apoptosis of Kaposi's sarcoma cells and of their putative endothelial precursors. , 2000, The Journal of investigative dermatology.

[66]  N. Burkhard,et al.  Photodegradation of atrazine, atraton and ametryne in aqueous solution with acetone as a photosensitiser , 1976 .

[67]  X. Lou,et al.  A novel folic acid-conjugated TiO₂-SiO₂ photosensitizer for cancer targeting in photodynamic therapy. , 2015, Colloids and surfaces. B, Biointerfaces.

[68]  J. Camacho,et al.  Cooperative magnetophoresis of superparamagnetic colloids: theoretical aspects , 2010 .

[69]  E. Greenberg,et al.  Sociomicrobiology: the connections between quorum sensing and biofilms. , 2005, Trends in microbiology.