{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T18:17:07Z","timestamp":1793038627801,"version":"4.5.0"},"reference-count":75,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,12,27]],"date-time":"2021-12-27T00:00:00Z","timestamp":1640563200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,12,27]],"date-time":"2021-12-27T00:00:00Z","timestamp":1640563200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001843","name":"Science and Engineering Research Board","doi-asserted-by":"publisher","award":["SR\/NM\/NS-41\/2016(G)"],"award-info":[{"award-number":["SR\/NM\/NS-41\/2016(G)"]}],"id":[{"id":"10.13039\/501100001843","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Diabetic foot infection caused by multidrug-resistant bacteria, is becoming serious problem. Moreover, polymicrobial biofilms contribute significantly to the persistent infections. In the present study, we investigated the effectiveness of novel toluidine blue conjugated chitosan coated gold\u2013silver core\u2013shell nanoparticles (TBO\u2013chit\u2013Au\u2013AgNPs) mediated photodynamic therapy and demonstrate their use as a nontoxic antibacterial therapy to combat diabetic foot ulcer (DFU) caused by multi-drug resistant strains both in monomicrobial and polymicrobial state of infection. In vitro efficacy of TBO\u2013chit\u2013Au\u2013AgNPs mediated photodynamic therapy (PDT) against polymicrobial biofilms was determined using standard plate count method and compared with that of monomicrobial biofilms of each species. Different anti-biofilm assays and microscopic studies were performed to check the efficacy of TBO\u2013chit\u2013Au\u2013AgNPs mediated PDT, displayed significant decrease in the formation of biofilm. Finally, its therapeutic potential was validated in vivo type-2DFU. Cytokines level was found reduced, using nano-phototheranostic approach, indicating infection control. Expression profile of growth factors confirmed both the pathogenesis and healing of DFU. Hence, we conclude that TBO\u2013chit\u2013Au\u2013AgNPs mediated PDT is a promising anti-bacterial therapeutic approach which leads to a synergistic healing of DFU caused by MDR bacterial strains.<\/jats:p>","DOI":"10.1038\/s41598-021-04008-x","type":"journal-article","created":{"date-parts":[[2021,12,27]],"date-time":"2021-12-27T11:08:06Z","timestamp":1640603286000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["A nano phototheranostic approach of toluidine blue conjugated gold silver core shells mediated photodynamic therapy to treat diabetic foot ulcer"],"prefix":"10.1038","volume":"11","author":[{"given":"Farheen","family":"Akhtar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asad U.","family":"Khan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bushra","family":"Qazi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Senthilguru","family":"Kulanthaivel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prashant","family":"Mishra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kafil","family":"Akhtar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asif","family":"Ali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,12,27]]},"reference":[{"key":"4008_CR1","doi-asserted-by":"crossref","unstructured":"Yu, C. O.-L., et al. The characterization of a full-thickness excision open foot wound model in n5-streptozotocin (STZ)-induced type 2 diabetic rats that mimics diabetic foot ulcer in terms of reduced blood circulation, higher C-reactive protein, elevated inflammation, and reduced cell proliferation.\u00a0Exp. Anim.\u00a066(3), 259\u2013269 (2017).","DOI":"10.1538\/expanim.17-0016"},{"issue":"9498","key":"4008_CR2","doi-asserted-by":"publisher","first-page":"1736","DOI":"10.1016\/S0140-6736(05)67700-8","volume":"366","author":"V Falanga","year":"2005","unstructured":"Falanga, V. Wound healing and its impairment in the diabetic foot. The Lancet 366(9498), 1736\u20131743 (2005).","journal-title":"The Lancet"},{"key":"4008_CR3","doi-asserted-by":"crossref","unstructured":"Kwon, K. T. & David, G. A. Microbiology and antimicrobial therapy for diabetic foot infections. Infect. Chemother. 50(1), 11\u201320 (2018).","DOI":"10.3947\/ic.2018.50.1.11"},{"key":"4008_CR4","doi-asserted-by":"crossref","unstructured":"Blakytny, R., and Jude, E. The molecular biology of chronic wounds and delayed healing in diabetes. Diabetic Med. 23, 594\u2013608 (2006).","DOI":"10.1111\/j.1464-5491.2006.01773.x"},{"key":"4008_CR5","doi-asserted-by":"crossref","unstructured":"Lan, C.\u2010C.E., et al. Hyperglycaemic conditions decrease cultured keratinocyte mobility: implications for impaired wound healing in patients with diabetes. Br. J. Dermatol. 159, 1103\u20131115 (2008).","DOI":"10.1111\/j.1365-2133.2008.08789.x"},{"key":"4008_CR6","doi-asserted-by":"crossref","unstructured":"Spollett, G. R. Preventing amputations in the diabetic population. Nurs. Clin. N. Am.\u00a033, 629\u2013641 (1998).","DOI":"10.1016\/S0029-6465(22)02629-9"},{"key":"4008_CR7","doi-asserted-by":"crossref","unstructured":"Dunne Jr, W. M. Bacterial adhesion: Seen any good biofilms lately?\u00a0Clin. Microbiol. Rev.\u00a015, 155\u2013166 (2002).","DOI":"10.1128\/CMR.15.2.155-166.2002"},{"key":"4008_CR8","unstructured":"Petersen, E. International Journal of Infectious Diseases. 16th International Congress on Infectious Diseases (ICID). Cape Town: Elsevier, 2014."},{"key":"4008_CR9","unstructured":"Lasa Uzcudun, \u00cd. Towards the identification of the common features of bacterial biofilm development.\u00a0Int. Microbiol. 9(1), 21\u201328\u00a0(2006)."},{"key":"4008_CR10","doi-asserted-by":"crossref","unstructured":"De la Fuente-N\u00fa\u00f1ez, C., et al. Broad-spectrum anti-biofilm peptide that targets a cellular stress response.\u00a0PLoS Pathog.\u00a010, e1004152 (2014).","DOI":"10.1371\/journal.ppat.1004152"},{"key":"4008_CR11","doi-asserted-by":"crossref","unstructured":"Lipsky, B. A., et al. Diagnosis and treatment of diabetic foot infections.\u00a0J. Am. Podiatr. Med. Assoc.\u00a095, 183\u2013210 (2005).","DOI":"10.7547\/0950183"},{"key":"4008_CR12","doi-asserted-by":"crossref","unstructured":"Stacy, A., et al. The biogeography of polymicrobial infection. Nat. Rev. Microbiol.14, 93\u2013105 (2016).","DOI":"10.1038\/nrmicro.2015.8"},{"key":"4008_CR13","doi-asserted-by":"crossref","unstructured":"Ferrer-Espada, R., et al. Antimicrobial blue light inactivation of polymicrobial biofilms. Front. Microb. 10, 721 (2019).","DOI":"10.3389\/fmicb.2019.00721"},{"key":"4008_CR14","doi-asserted-by":"crossref","unstructured":"DeLeon, S., et al. Synergistic interactions of Pseudomonas aeruginosa and Staphylococcus aureus in an in vitro wound model. Infect. Immun. 82, 4718\u20134728 (2014).","DOI":"10.1128\/IAI.02198-14"},{"issue":"14","key":"4008_CR15","doi-asserted-by":"publisher","first-page":"6141","DOI":"10.1007\/s00253-016-7596-3","volume":"100","author":"AT Nguyen","year":"2016","unstructured":"Nguyen, A. T. & Oglesby-Sherrouse, A. G. Interactions between Pseudomonas aeruginosa and Staphylococcus aureus during co-cultivations and polymicrobial infections. Appl. Microbiol. Biotechnol. 100(14), 6141\u20136148 (2016).","journal-title":"Appl. Microbiol. Biotechnol."},{"issue":"2","key":"4008_CR16","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1111\/j.1469-0691.2012.04001.x","volume":"19","author":"R Wolcott","year":"2013","unstructured":"Wolcott, R. et al. The polymicrobial nature of biofilm infection. Clin. Microbiol. Infect. 19(2), 107\u2013112 (2013).","journal-title":"Clin. Microbiol. Infect."},{"key":"4008_CR17","doi-asserted-by":"crossref","unstructured":"Parveen, S., Misra, R. & Sahoo, S. K. Nanoparticles: a boon to drug delivery, therapeutics, diagnostics and imaging. Nanomed. Nanotechnol. Biol. Med.\u00a08, 147\u2013166 (2012).","DOI":"10.1016\/j.nano.2011.05.016"},{"key":"4008_CR18","doi-asserted-by":"crossref","unstructured":"Gold, K., et al. Antimicrobial activity of metal and metal\u2010oxide based nanoparticles.\u00a0Adv. Ther.\u00a01, 1700033 (2018).","DOI":"10.1002\/adtp.201700033"},{"key":"4008_CR19","doi-asserted-by":"crossref","unstructured":"He, J., et al. Gold\u2013silver nanoshells promote wound healing from drug-resistant bacteria infection and enable monitoring via surface-enhanced Raman scattering imaging.\u00a0Biomater.\u00a0234, 119763 (2020).","DOI":"10.1016\/j.biomaterials.2020.119763"},{"issue":"7","key":"4008_CR20","doi-asserted-by":"publisher","first-page":"1169","DOI":"10.4314\/tjpr.v13i7.23","volume":"13","author":"AK Khan","year":"2014","unstructured":"Khan, A. K. et al. Gold nanoparticles: Synthesis and applications in drug delivery. Trop. J. Pharm. Res. 13(7), 1169\u20131177 (2014).","journal-title":"Trop. J. Pharm. Res."},{"key":"4008_CR21","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1016\/j.jphotobiol.2015.12.002","volume":"154","author":"D Dhamecha","year":"2016","unstructured":"Dhamecha, D., Jalalpure, S. & Jadhav, K. Nepenthes khasiana mediated synthesis of stabilized gold nanoparticles: Characterization and biocompatibility studies. J. Photochem. Photobiol. B 154, 108\u2013117 (2016).","journal-title":"J. Photochem. Photobiol. B"},{"key":"4008_CR22","doi-asserted-by":"crossref","unstructured":"Giljohann, D. A., et al. Gold nanoparticles for biology and medicine. Angew. Chem. Int. Edn.\u00a049, 3280\u20133294 (2010).","DOI":"10.1002\/anie.200904359"},{"key":"4008_CR23","doi-asserted-by":"crossref","unstructured":"Salem, D. S., et al. Improved chemo-photothermal therapy of hepatocellular carcinoma using chitosan\u2013coated gold nanoparticles. J. Photochem. Photobiol. B 182, 92\u201399 (2018).","DOI":"10.1016\/j.jphotobiol.2018.03.024"},{"key":"4008_CR24","doi-asserted-by":"crossref","unstructured":"Hada, A.-M., et al. Fabrication of gold\u2013silver core\u2013shell nanoparticles for performing as ultrabright SERS-nanotags inside human ovarian cancer cells. Nanotechnol. 30, 315701 (2019).","DOI":"10.1088\/1361-6528\/ab1857"},{"key":"4008_CR25","doi-asserted-by":"crossref","unstructured":"Sondi, I. & Branka, S.-S. Silver nanoparticles as antimicrobial agent: A case study on E. coli as a model for Gram-negative bacteria. J. Colloid Interface Sci. 275, 177\u2013182 (2004).","DOI":"10.1016\/j.jcis.2004.02.012"},{"key":"4008_CR26","doi-asserted-by":"crossref","unstructured":"Potara, M., et al. Synergistic antibacterial activity of chitosan\u2013silver nanocomposites on Staphylococcus aureus. Nanotechnology\u00a022, 135101 (2011).","DOI":"10.1088\/0957-4484\/22\/13\/135101"},{"key":"4008_CR27","doi-asserted-by":"crossref","unstructured":"Morones, J. R., et al.The bactericidal effect of silver nanoparticles. Nanotechnol. 16, 2346 (2005).","DOI":"10.1088\/0957-4484\/16\/10\/059"},{"key":"4008_CR28","doi-asserted-by":"crossref","unstructured":"Li, Q., et al. Antimicrobial nanomaterials for water disinfection and microbial control: potential applications and implications. Water Res. 42, 4591\u20134602 (2008).","DOI":"10.1016\/j.watres.2008.08.015"},{"key":"4008_CR29","doi-asserted-by":"crossref","unstructured":"Rabea, E. I., et al. Chitosan as antimicrobial agent: Applications and mode of action.\u00a0Biomacromolecules 4, 1457\u20131465 (2003).","DOI":"10.1021\/bm034130m"},{"key":"4008_CR30","doi-asserted-by":"crossref","unstructured":"Chen, Q., et al. Preparation, antibacterial, and antioxidant activities of silver\/chitosan composites. J. Carbohydr. Chem.\u00a033, 298\u2013312 (2014).","DOI":"10.1080\/07328303.2014.931962"},{"key":"4008_CR31","doi-asserted-by":"crossref","unstructured":"Sharma, M., et al. Toluidine blue-mediated photodynamic effects on staphylococcal biofilms. Antimicrob. Agents Chemother. 52, 299\u2013305 (2008).","DOI":"10.1128\/AAC.00988-07"},{"issue":"6","key":"4008_CR32","doi-asserted-by":"publisher","first-page":"2329","DOI":"10.1128\/AAC.49.6.2329-2335.2005","volume":"49","author":"TN Demidova","year":"2005","unstructured":"Demidova, T. N. & Hamblin, M. R. Effect of cell-photosensitizer binding and cell density on microbial photoinactivation. Antimicrob. Agents Chemother. 49(6), 2329\u20132335 (2005).","journal-title":"Antimicrob. Agents Chemother."},{"key":"4008_CR33","doi-asserted-by":"crossref","unstructured":"Usacheva, M. N., Teichert, M. C. & Biel, M. A. Comparison of the methylene blue and toluidine blue photobactericidal efficacy against gram\u2010positive and gram\u2010negative microorganisms.\u00a0Lasers Surg. Med. 29, 165\u2013173 (2001).","DOI":"10.1002\/lsm.1105"},{"issue":"1","key":"4008_CR34","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1093\/jac\/42.1.13","volume":"42","author":"M Wainwright","year":"1998","unstructured":"Wainwright, M. Photodynamic antimicrobial chemotherapy (PACT). J. Antimicrob. Chemother. 42(1), 13\u201328 (1998).","journal-title":"J. Antimicrob. Chemother."},{"key":"4008_CR35","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.pdpdt.2017.01.177","volume":"18","author":"L Misba","year":"2017","unstructured":"Misba, L., Zaidi, S. & Khan, A. U. A comparison of antibacterial and antibiofilm efficacy of phenothiazinium dyes between Gram positive and Gram negative bacterial biofilm. Photodiagn. Photodyn. Ther. 18, 24\u201333 (2017).","journal-title":"Photodiagn. Photodyn. Ther."},{"key":"4008_CR36","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1016\/j.pdpdt.2019.05.001","volume":"26","author":"L Misba","year":"2019","unstructured":"Misba, L., Abdulrahman, H. & Khan, A. U. Photodynamic efficacy of toluidine blue O against mono species and dual species bacterial biofilm. Photodiagn. Photodyn. Ther. 26, 383\u2013388 (2019).","journal-title":"Photodiagn. Photodyn. Ther."},{"key":"4008_CR37","doi-asserted-by":"crossref","unstructured":"Costa, L., et al. Involvement of type I and type II mechanisms on the photoinactivation of non-enveloped DNA and RNA bacteriophages. J. Photochem. Photobiol. B 120, 10\u201316 (2013).","DOI":"10.1016\/j.jphotobiol.2013.01.005"},{"key":"4008_CR38","doi-asserted-by":"crossref","unstructured":"Carvalho, C. M. B., et al. Photoinactivation of bacteria in wastewater by porphyrins: Bacterial \u03b2-galactosidase activity and leucine-uptake as methods to monitor the process. J. Photochem. Photobiol. B 88, 112\u2013118 (2007).","DOI":"10.1016\/j.jphotobiol.2007.04.015"},{"key":"4008_CR39","doi-asserted-by":"crossref","unstructured":"Almeida, A., Faustino, M. A. F. & Tom\u00e9, J. P. C.. Photodynamic inactivation of bacteria: Finding the effective targets. Future Med. Chem. 7, 1221\u20131224 (2015).","DOI":"10.4155\/fmc.15.59"},{"issue":"5","key":"4008_CR40","doi-asserted-by":"publisher","first-page":"436","DOI":"10.1039\/b311900a","volume":"3","author":"MR Hamblin","year":"2004","unstructured":"Hamblin, M. R. & Hasan, T. Photodynamic therapy: A new antimicrobial approach to infectious disease?. Photochem. Photobiol. Sci. 3(5), 436\u2013450 (2004).","journal-title":"Photochem. Photobiol. Sci."},{"key":"4008_CR41","doi-asserted-by":"crossref","unstructured":"Costa, L., et al. Photodynamic inactivation of mammalian viruses and bacteriophages. Viruses\u00a04, 1034\u20131074 (2012).","DOI":"10.3390\/v4071034"},{"key":"4008_CR42","doi-asserted-by":"crossref","unstructured":"da Silva, Raquel N., et al. Photo\u2010inactivation of Bacillus endospores: Inter\u2010specific variability of inactivation efficiency. Microbiol. Immunol. 56, 692\u2013699 (2012).","DOI":"10.1111\/j.1348-0421.2012.00493.x"},{"issue":"5","key":"4008_CR43","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1039\/b614770d","volume":"6","author":"T Maisch","year":"2007","unstructured":"Maisch, T. et al. Determination of the antibacterial efficacy of a new porphyrin-based photosensitizer against MRSA ex vivo. Photochem. Photobiol. Sci. 6(5), 545\u2013551 (2007).","journal-title":"Photochem. Photobiol. Sci."},{"key":"4008_CR44","doi-asserted-by":"crossref","unstructured":"Rodrigues, G. B., et al. Susceptibilities of the dermatophytes Trichophyton mentagrophytes and T. rubrum microconidia to photodynamic antimicrobial chemotherapy with novel phenothiazinium photosensitizers and red light.\u00a0J. Photochem. Photobiol. B\u00a0116, 89\u201394 (2012).","DOI":"10.1016\/j.jphotobiol.2012.08.010"},{"key":"4008_CR45","doi-asserted-by":"crossref","unstructured":"Rodrigues, G. B., et al. In vitro photodynamic inactivation of Candida species and mouse fibroblasts with phenothiazinium photosensitisers and red light. Photodiagn. Photodyn. Ther.\u00a010, 141\u2013149 (2013).","DOI":"10.1016\/j.pdpdt.2012.11.004"},{"key":"4008_CR46","doi-asserted-by":"crossref","unstructured":"Beirao, S., et al. Photodynamic inactivation of bacterial and yeast biofilms with a cationic porphyrin. Photochem. Photobiol. 90, 1387\u20131396 (2014).","DOI":"10.1111\/php.12331"},{"key":"4008_CR47","doi-asserted-by":"crossref","unstructured":"Cieplik, F., et al. Antimicrobial photodynamic therapy\u2014what we know and what we don\u2019t. Crit. Rev. Microbiol. 44, 571\u2013589 (2018).","DOI":"10.1080\/1040841X.2018.1467876"},{"key":"4008_CR48","doi-asserted-by":"crossref","unstructured":"Huang, Y.-Y., et al. Antimicrobial photodynamic therapy mediated by methylene blue and potassium iodide to treat urinary tract infection in a female rat model. Sci. Rep. 8, 1\u20139 (2018).","DOI":"10.1038\/s41598-018-25365-0"},{"key":"4008_CR49","doi-asserted-by":"crossref","unstructured":"Khan, S., et al. Photoinactivation of multidrug resistant bacteria by monomeric methylene blue conjugated gold nanoparticles. J. Photochem. Photobiol. B\u00a0174, 150\u2013161 (2017).","DOI":"10.1016\/j.jphotobiol.2017.07.011"},{"key":"4008_CR50","doi-asserted-by":"crossref","unstructured":"Akhtar, F., et al. Antimicrobial and antibiofilm photodynamic therapy against vancomycin resistant Staphylococcus aureus (VRSA) induced infection in vitro and in vivo. Eur. J. Pharmaceut Biopharmaceut\u00a0160, 65\u201376 (2021).","DOI":"10.1016\/j.ejpb.2021.01.012"},{"key":"4008_CR51","doi-asserted-by":"crossref","unstructured":"Ahmed, D. N., et al. Waste foundry sand\/MgFe-layered double hydroxides composite material for efficient removal of Congo red dye from aqueous solution.\u00a0Sci. Rep. 10, 1\u201312 (2020).","DOI":"10.1038\/s41598-020-58866-y"},{"key":"4008_CR52","doi-asserted-by":"crossref","unstructured":"Zhang, X., et al. Mass production of poly(ethylene glycol) monooleate-modified core\u2013shell structured upconversion nanoparticles for bio-imaging and photodynamic therapy. Sci. Rep. 9, 1\u201310 (2019).","DOI":"10.1038\/s41598-019-41482-w"},{"key":"4008_CR53","doi-asserted-by":"crossref","unstructured":"Lu, L., et al. Core\u2013shell gold\/silver nanoparticles: Synthesis and optical properties. J. Colloid Interface Sci. 392, 90\u201395 (2013).","DOI":"10.1016\/j.jcis.2012.09.057"},{"key":"4008_CR54","doi-asserted-by":"crossref","unstructured":"Kumar, M. N. V. Ravi, et al. Chitosan chemistry and pharmaceutical perspectives. Chem. Rev. 104, 6017\u20136084 (2004).","DOI":"10.1021\/cr030441b"},{"issue":"4","key":"4008_CR55","doi-asserted-by":"publisher","first-page":"437","DOI":"10.2217\/fmb-2017-0207","volume":"13","author":"L Misba","year":"2018","unstructured":"Misba, L. & Khan, A. U. Enhanced photodynamic therapy using light fractionation against Streptococcus mutans biofilm: Type I and type II mechanism. Future Microbiol. 13(4), 437\u2013454 (2018).","journal-title":"Future Microbiol."},{"key":"4008_CR56","doi-asserted-by":"crossref","unstructured":"Caudill, Emily R., et al. Wall teichoic acids govern cationic gold nanoparticle interaction with Gram-positive bacterial cell walls. Chem. Sci. 11, 4106\u20134118 (2020).","DOI":"10.1039\/C9SC05436G"},{"key":"4008_CR57","doi-asserted-by":"crossref","unstructured":"Kim, S. Y., Kwon, O. J. & Park, J.-W. Inactivation of catalase and superoxide dismutase by singlet oxygen derived from photoactivated dye.\u00a0Biochimie\u00a083, 437\u2013444 (2001).","DOI":"10.1016\/S0300-9084(01)01258-5"},{"key":"4008_CR58","doi-asserted-by":"crossref","unstructured":"Pereira, C. A., et al. Susceptibility of Candida albicans, Staphylococcus aureus, and Streptococcus mutans biofilms to photodynamic inactivation: an in vitro study. Lasers Med. Sci.\u00a026, 341\u2013348 (2011).","DOI":"10.1007\/s10103-010-0852-3"},{"issue":"S1","key":"4008_CR59","doi-asserted-by":"publisher","first-page":"13S","DOI":"10.1111\/j.1365-2672.1998.tb05278.x","volume":"85","author":"LC Skillman","year":"1998","unstructured":"Skillman, L. C., Sutherland, I. W. & Jones, M. V. The role of exopolysaccharides in dual species biofilm development. J. Appl. Microbiol. 85(S1), 13S-18S (1998).","journal-title":"J. Appl. Microbiol."},{"key":"4008_CR60","doi-asserted-by":"crossref","unstructured":"Vlassara, H., et al. Identification of galectin-3 as a high-affinity binding protein for advanced glycation end products (AGE): A new member of the AGE-receptor complex.\u00a0Mol. Med.\u00a01, 634\u2013646 (1995).","DOI":"10.1007\/BF03401604"},{"key":"4008_CR61","doi-asserted-by":"crossref","unstructured":"Ojalvo, A. G., et al. Healing enhancement of diabetic wounds by locally infiltrated epidermal growth factor is associated with systemic oxidative stress reduction.\u00a0Int. Wound J.\u00a014, 214\u2013225 (2017).","DOI":"10.1111\/iwj.12592"},{"key":"4008_CR62","doi-asserted-by":"crossref","unstructured":"Gardner, J. C., et al. Keratinocyte growth factor supports pulmonary innate immune defense through maintenance of alveolar antimicrobial protein levels and macrophage function. Am. J. Physiol. Lung Cell. Mol. Physiol. 310, L868\u2013L879 (2016).","DOI":"10.1152\/ajplung.00363.2015"},{"issue":"2","key":"4008_CR63","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1007\/s11154-019-09492-1","volume":"20","author":"M Zubair","year":"2019","unstructured":"Zubair, M. & Ahmad, J. Role of growth factors and cytokines in diabetic foot ulcer healing: A detailed review. Rev. Endocr. Metab. Disord. 20(2), 207\u2013217 (2019).","journal-title":"Rev. Endocr. Metab. Disord."},{"key":"4008_CR64","doi-asserted-by":"crossref","unstructured":"Aldea, M., et al. Metformin delivery using chitosan\u2013capped gold nanoparticles in glioblastoma cell lines. Roman. Neurosurg. 230\u2013239 (2018).","DOI":"10.2478\/romneu-2018-0030"},{"key":"4008_CR65","doi-asserted-by":"crossref","unstructured":"Samal, A. K., et al. Size tunable Au@ Ag core\u2013shell nanoparticles: Synthesis and surface-enhanced Raman scattering properties. Langmuir\u00a029, 15076\u201315082 (2013).","DOI":"10.1021\/la403707j"},{"key":"4008_CR66","doi-asserted-by":"crossref","unstructured":"Rolim, J. P. M. L., et al. The antimicrobial activity of photodynamic therapy against Streptococcus mutans using different photosensitizers. J. Photochem. Photobiol. B\u00a0106, 40\u201346 (2012).","DOI":"10.1016\/j.jphotobiol.2011.10.001"},{"key":"4008_CR67","doi-asserted-by":"crossref","unstructured":"Misba, L., Kulshrestha, S. & Khan, A. U. Antibiofilm action of a toluidine blue O-silver nanoparticle conjugate on Streptococcus mutans: A mechanism of type I photodynamic therapy. Biofouling\u00a032, 313\u2013328 (2016).","DOI":"10.1080\/08927014.2016.1141899"},{"issue":"1","key":"4008_CR68","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1073\/pnas.1315053111","volume":"111","author":"J Chen","year":"2014","unstructured":"Chen, J., Cesario, T. C. & Rentzepis, P. M. Rationale and mechanism for the low photoinactivation rate of bacteria in plasma. Proc. Natl. Acad. Sci. 111(1), 33\u201338 (2014).","journal-title":"Proc. Natl. Acad. Sci."},{"key":"4008_CR69","doi-asserted-by":"crossref","unstructured":"Kulshrestha, S., et al. Calcium fluoride nanoparticles induced suppression of Streptococcus mutans biofilm: An in vitro and in vivo approach. Appl. Microbiol. Biotechnol. 100, 1901\u20131914 (2016).","DOI":"10.1007\/s00253-015-7154-4"},{"key":"4008_CR70","doi-asserted-by":"crossref","unstructured":"L\u00f3pez-Moreno, A., et al. Calcium carbonate precipitation by heterotrophic bacteria isolated from biofilms formed on deteriorated ignimbrite stones: Influence of calcium on EPS production and biofilm formation by these isolates. Biofouling\u00a030, 547\u2013560 (2014).","DOI":"10.1080\/08927014.2014.888715"},{"key":"4008_CR71","doi-asserted-by":"crossref","unstructured":"Senapati, .V A., et al. ZnO nanoparticles induced inflammatory response and genotoxicity in human blood cells: A mechanistic approach. Food Chem. Toxicol. 85, 61\u201370 (2015).","DOI":"10.1016\/j.fct.2015.06.018"},{"issue":"1","key":"4008_CR72","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1159\/000122834","volume":"41","author":"TW Lau","year":"2008","unstructured":"Lau, T. W. et al. An in vivo investigation on the wound-healing effect of two medicinal herbs using an animal model with foot ulcer. Eur. Surg. Res. 41(1), 15\u201323 (2008).","journal-title":"Eur. Surg. Res."},{"key":"4008_CR73","doi-asserted-by":"crossref","unstructured":"Tawfik, A. A. et al. A study of the treatment of cutaneous fungal infection in animal model using photoactivated composite of methylene blue and gold nanoparticle. Photodiagn. Photodyn. Ther. 15, 59\u201369 (2016).","DOI":"10.1016\/j.pdpdt.2016.05.010"},{"key":"4008_CR74","doi-asserted-by":"crossref","unstructured":"Karamese, M., et al. Anti-oxidant and anti-inflammatory effects of apigenin in a rat model of sepsis: an immunological, biochemical, and histopathological study. Immunopharmacol. Immunotoxicol.\u00a038.3, 228\u2013237 (2016).","DOI":"10.3109\/08923973.2016.1173058"},{"key":"4008_CR75","unstructured":"ANOVA: Analysis OfVAriance between groups. www.physics.csbsju.edu\/stats\/anova.html"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-04008-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-04008-x","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-04008-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,3]],"date-time":"2022-12-03T18:34:02Z","timestamp":1670092442000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-04008-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,27]]},"references-count":75,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["4008"],"URL":"https:\/\/doi.org\/10.1038\/s41598-021-04008-x","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,27]]},"assertion":[{"value":"1 June 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 November 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 December 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"24464"}}