{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T21:01:49Z","timestamp":1788469309700,"version":"build-2803163510"},"reference-count":60,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T00:00:00Z","timestamp":1669852800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004919","name":"National Plan for Science, Technology and Innovation (MAARIFAH), King Abdulaziz City for Science and Technology, Kingdom of Saudi Arabia","doi-asserted-by":"publisher","award":["14-NAN-862-02"],"award-info":[{"award-number":["14-NAN-862-02"]}],"id":[{"id":"10.13039\/501100004919","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cancer is a leading cause of death worldwide. Conventional methods of cancer treatment, including chemotherapy and radiotherapy, are associated with multiple side effects. Recently, photodynamic therapy (PDT) has emerged as an effective therapeutic modality for cancer treatment without adversely affecting normal tissue. In this study, we synthesized nitrogen doped graphene (NDG) and conjugated it with Mn3O4 nanoparticles to produce NDG-Mn3O4 nanocomposite with the aim of testing its bimodal performance including PDT and magnetic resonance imaging (MRI). We did not use any linker or binder for conjugation between NDG and Mn3O4, rather they were anchored by a milling process. The results of cell viability analysis showed that NDG-Mn3O4 nanocomposites caused significant cell death under laser irradiation, while control and Mn3O4 nanoparticles showed negligible cell death. We observed increased generation of singlet oxygen after exposure of NDG-Mn3O4 nanocomposites, which was directly proportional to the duration of laser irradiation. The results of MRI showed concentration dependent enhancement of signal intensity with an increasing concentration of NDG-Mn3O4 nanocomposites. In conclusion, NDG-Mn3O4 nanocomposites did not cause any cytotoxicity under physiological conditions. However, they produced significant and dose-dependent cytotoxicity in cancer cells after laser irradiation. NDG-Mn3O4 nanocomposites also exhibited concentration-dependent MRI contrast property, suggesting their possible application for cancer imaging. Further studies are warranted to test the theranostic potential of NDG-Mn3O4 nanocomposites using animal models of cancer.<\/jats:p>","DOI":"10.3390\/ijms232315087","type":"journal-article","created":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T05:03:18Z","timestamp":1669870998000},"page":"15087","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Nanocomposites of Nitrogen-Doped Graphene Oxide and Manganese Oxide for Photodynamic Therapy and Magnetic Resonance Imaging"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6084-8589","authenticated-orcid":false,"given":"Haseeb A.","family":"Khan","sequence":"first","affiliation":[{"name":"Department of Biochemistry, College of Science, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong-Kyu","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Chemical and Biological Engineering, Korea National University of Transportation, Chungju, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2937-317X","authenticated-orcid":false,"given":"Mohammed Rafi","family":"Shaik","sequence":"additional","affiliation":[{"name":"Department of Chemistry, College of Science, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara T.","family":"Alrashood","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8024-0631","authenticated-orcid":false,"given":"Aishah A.","family":"Ekhzaimy","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Department of Medicine, King Khalid University Hospital, Riyadh 11472, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1937","DOI":"10.1166\/jbn.2014.1953","article-title":"Photodynamic therapy: One step ahead with self-assembled nanoparticles","volume":"10","author":"Avci","year":"2014","journal-title":"J. Biomed. Nanotechnol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1016\/j.biopha.2018.07.049","article-title":"Photodynamic therapy\u2014Mechanisms, photosensitizers and combinations","volume":"106","author":"Kwiatkowski","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Sun, J., Kormakov, S., Liu, Y., Huang, Y., Wu, D., and Yang, Z. (2018). Recent progress in metal-based nanoparticles mediated photodynamic therapy. Molecules, 23.","DOI":"10.3390\/molecules23071704"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"5633","DOI":"10.2147\/IJN.S316471","article-title":"Sol\u2013gel synthesis of dy-substituted Ni0.4Cu0.2Zn0.4 (Fe2-xDyx)O4 nano spinel ferrites and evaluation of their antibacterial, antifungal, antibiofilm and anticancer potentialities for biomedical application","volume":"16","author":"Ansari","year":"2021","journal-title":"Int. J. Nanomed."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1887","DOI":"10.2174\/1568026615666150506145251","article-title":"Metal oxide nanomaterials in nanomedicine: Applications in photodynamic therapy and potential toxicity","volume":"15","author":"He","year":"2015","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"6620","DOI":"10.1021\/nn501652j","article-title":"Targeted iron-oxide nanoparticle for photodynamic therapy and imaging of head and neck cancer","volume":"8","author":"Wang","year":"2014","journal-title":"ACS Nano"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12951-022-01441-6","article-title":"Tumor microenvironment responsive Mn3O4 nanoplatform for in vivo real-time monitoring of drug resistance and photothermal\/chemodynamic synergistic therapy of gastric cancer","volume":"20","author":"Li","year":"2022","journal-title":"J. Nanobiotechnol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"5270","DOI":"10.1039\/C3NR05687B","article-title":"Redox-mediated dissolution of paramagnetic nanolids to achieve a smart theranostic system","volume":"6","author":"Wang","year":"2014","journal-title":"Nanoscale"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"5397","DOI":"10.1002\/anie.200604775","article-title":"Development of a T1 contrast agent for magnetic resonance imaging using MnO nanoparticles","volume":"46","author":"Na","year":"2007","journal-title":"Angew. Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"30216","DOI":"10.1039\/C9RA06835J","article-title":"Novel one pot synthesis and spectroscopic characterization of a folate-Mn3O4 nanohybrid for potential photodynamic therapeutic application","volume":"9","author":"Mondal","year":"2019","journal-title":"RSC Adv."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"4058","DOI":"10.1002\/adfm.201100840","article-title":"Design guidelines for conjugated polymers with light-activated anticancer activity","volume":"21","author":"Xing","year":"2011","journal-title":"Adv. Funct. Mater."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"101830","DOI":"10.1016\/j.jddst.2020.101830","article-title":"Two-dimensional (2D) materials beyond graphene in cancer drug delivery, photothermal and photodynamic therapy, recent advances and challenges ahead: A review","volume":"61","author":"Molaei","year":"2021","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"18753","DOI":"10.1039\/C5TA02240A","article-title":"Graphene based metal and metal oxide nanocomposites: Synthesis, properties and their applications","volume":"3","author":"Khan","year":"2015","journal-title":"J. Mater. Chem. A"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1016\/j.pmatsci.2012.03.002","article-title":"Chemical functionalization of graphene and its applications","volume":"57","author":"Kuila","year":"2012","journal-title":"Prog. Mater. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"10876","DOI":"10.1021\/ja803688x","article-title":"PEGylated nanographene oxide for delivery of water-insoluble cancer drugs","volume":"130","author":"Liu","year":"2008","journal-title":"J. Am. Chem. Soc."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1021\/tx200339h","article-title":"Biological interactions of graphene-family nanomaterials: An interdisciplinary review","volume":"25","author":"Sanchez","year":"2012","journal-title":"Chem. Res. Toxicol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"9308","DOI":"10.1039\/c2jm16678j","article-title":"Fluorescent graphene oxide composites synthesis and its biocompatibility study","volume":"22","author":"Xie","year":"2012","journal-title":"J. Mater. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1038\/nnano.2007.451","article-title":"Processable aqueous dispersions of graphene nanosheets","volume":"3","author":"Li","year":"2008","journal-title":"Nat. Nanotechnol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1021\/ar300199e","article-title":"Safety considerations for graphene: Lessons learnt from carbon nanotubes","volume":"46","author":"Bussy","year":"2013","journal-title":"Acc. Chem. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.electacta.2012.07.022","article-title":"N-doped graphene\/carbon composite as non-precious metal electrocatalyst for oxygen reduction reaction","volume":"81","author":"Liu","year":"2012","journal-title":"Electrochim. Acta"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1007\/s12274-019-2337-4","article-title":"Nitrogen-doped graphene quantum dots: Optical properties modification and photovoltaic applications","volume":"12","author":"Hasan","year":"2019","journal-title":"Nano Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4169","DOI":"10.1021\/am508416n","article-title":"Nitrogen-doped graphene for generation and evolution of reactive radicals by metal-free catalysis","volume":"7","author":"Duan","year":"2015","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1520","DOI":"10.3866\/PKU.WHXB201203131","article-title":"Cell biocompatibility of functionalized graphene oxide","volume":"28","author":"Zhang","year":"2012","journal-title":"Acta Phys. Chim. Sin."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.jconrel.2016.02.015","article-title":"Assessing biocompatibility of graphene oxide-based nanocarriers: A review","volume":"226","author":"Kiew","year":"2016","journal-title":"J. Control. Release"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"4040","DOI":"10.1016\/j.carbon.2011.05.056","article-title":"In vitro and in vivo behaviors of dextran functionalized graphene","volume":"49","author":"Zhang","year":"2011","journal-title":"Carbon"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1704","DOI":"10.1166\/jnn.2017.12825","article-title":"Peptide-influenced graphene quantum dots on iron oxide nanoparticles for dual imaging of lung cancer cells","volume":"17","author":"Nafiujjaman","year":"2017","journal-title":"J. Nanosci. Nanotechnol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"42141","DOI":"10.1039\/C5RA04756K","article-title":"Bioapplication of graphene oxide derivatives: Drug\/gene delivery, imaging, polymeric modification, toxicology, therapeutics and challenges","volume":"5","author":"Nurunnabi","year":"2015","journal-title":"RSC Adv."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"8321","DOI":"10.2147\/IJN.S218085","article-title":"Manganese oxide nanoparticles as MRI contrast agents in tumor multimodal imaging and therapy","volume":"14","author":"Cai","year":"2019","journal-title":"Int. J. Nanomed."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"34954","DOI":"10.1021\/acsami.8b12355","article-title":"Polyethyleneimine-coated manganese oxide nanoparticles for targeted tumor PET\/MR imaging","volume":"10","author":"Zhu","year":"2018","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00339-021-04428-6","article-title":"Dye degradation studies of hausmannite manganese oxide (Mn3O4) nanoparticles synthesized by chemical method","volume":"127","author":"Wang","year":"2021","journal-title":"Appl. Phys. A"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1016\/S1386-1425(03)00279-8","article-title":"Lattice vibrations of manganese oxides: Part I. Periodic structures","volume":"60","author":"Julien","year":"2004","journal-title":"Spectrochim. Acta Part A Mol. Biomol. Spectrosc."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3183","DOI":"10.1166\/jnn.2021.19355","article-title":"Effective chemical vapor deposition and characterization of N-doped graphene for high electrochemical performance","volume":"21","author":"Mahalingam","year":"2021","journal-title":"J. Nanosci. Nanotechnol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2263","DOI":"10.1002\/celc.201800520","article-title":"Growth of MoS2 nanoflowers with expanded interlayer distance onto N-doped graphene for reversible lithium storage","volume":"5","author":"Wu","year":"2018","journal-title":"ChemElectroChem"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"5815","DOI":"10.1039\/C5TB00479A","article-title":"Ternary graphene quantum dot\u2013polydopamine\u2013Mn3O4 nanoparticles for optical imaging guided photodynamic therapy and T 1-weighted magnetic resonance imaging","volume":"3","author":"Nafiujjaman","year":"2015","journal-title":"J. Mater. Chem. B"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3195","DOI":"10.1039\/c0cc05005a","article-title":"Biocompatible reduced graphene oxide prepared by using dextran as a multifunctional reducing agent","volume":"47","author":"Kim","year":"2011","journal-title":"Chem. Commun."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"4085","DOI":"10.1021\/am2009647","article-title":"Composites of aminodextran-coated Fe3O4 nanoparticles and graphene oxide for cellular magnetic resonance imaging","volume":"3","author":"Chen","year":"2011","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1159\/000362416","article-title":"Photodynamic therapy: Current status and future directions","volume":"24","author":"Benov","year":"2015","journal-title":"Med. Princ. Pract."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"7","DOI":"10.5946\/ce.2013.46.1.7","article-title":"Advance in photosensitizers and light delivery for photodynamic therapy","volume":"46","author":"Yoon","year":"2013","journal-title":"Clin. Endosc."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1517\/17425247.2012.729575","article-title":"The application of graphene oxide in drug delivery","volume":"9","author":"Pan","year":"2012","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"4013","DOI":"10.1016\/j.biomaterials.2012.02.021","article-title":"The role of the lateral dimension of graphene oxide in the regulation of cellular responses","volume":"33","author":"Yue","year":"2012","journal-title":"Biomaterials"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1007\/s12274-008-8021-8","article-title":"Nano-graphene oxide for cellular imaging and drug delivery","volume":"1","author":"Sun","year":"2008","journal-title":"Nano Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"3407","DOI":"10.1021\/cr300335p","article-title":"Graphene: Promises, facts, opportunities, and challenges in nanomedicine","volume":"113","author":"Mao","year":"2013","journal-title":"Chem. Rev."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"415101","DOI":"10.1088\/0957-4484\/23\/41\/415101","article-title":"Cellular imaging using biocompatible dendrimer-functionalized graphene oxide-based fluorescent probe anchored with magnetic nanoparticles","volume":"23","author":"Wate","year":"2012","journal-title":"Nanotechnology"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"465103","DOI":"10.1088\/0957-4484\/23\/46\/465103","article-title":"Cell uptake survey of pegylated nanographene oxide","volume":"23","author":"Vila","year":"2012","journal-title":"Nanotechnology"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"6735","DOI":"10.1021\/nn403096s","article-title":"Photothermally triggered cytosolic drug delivery via endosome disruption using a functionalized reduced graphene oxide","volume":"7","author":"Kim","year":"2013","journal-title":"ACS Nano"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"3624","DOI":"10.1021\/acsami.5b07995","article-title":"Amplified singlet oxygen generation in semiconductor polymer dots for photodynamic cancer therapy","volume":"8","author":"Li","year":"2016","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"16686","DOI":"10.1021\/jacs.6b09538","article-title":"Photodynamic therapy mediated by nontoxic core\u2013shell nanoparticles synergizes with immune checkpoint blockade to elicit antitumor immunity and antimetastatic effect on breast cancer","volume":"138","author":"Duan","year":"2016","journal-title":"J. Am. Chem. Soc."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.2147\/JIR.S275595","article-title":"Reactive oxygen species: Drivers of physiological and pathological processes","volume":"13","author":"Checa","year":"2020","journal-title":"J. Inflamm. Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2181","DOI":"10.1007\/s00018-007-7230-8","article-title":"Biological redox systems and oxidative stress","volume":"64","author":"Sies","year":"2007","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"156","DOI":"10.7150\/ntno.33536","article-title":"Near-infrared organic fluorescent nanoparticles for long-term monitoring and photodynamic therapy of cancer","volume":"3","author":"Xia","year":"2019","journal-title":"Nanotheranostics"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1016\/j.apsb.2020.07.021","article-title":"A smart MnO2-doped graphene oxide nanosheet for enhanced chemo-photodynamic combinatorial therapy via simultaneous oxygenation and glutathione depletion","volume":"11","author":"Liu","year":"2021","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"6725","DOI":"10.1039\/C6CS00442C","article-title":"Two-photon excitation nanoparticles for photodynamic therapy","volume":"45","author":"Shen","year":"2016","journal-title":"Chem. Soc. Rev."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"14061","DOI":"10.1039\/D0NR03398G","article-title":"Cyclometalated iridium (III) complex nanoparticles for mitochondria-targeted photodynamic therapy","volume":"12","author":"Lu","year":"2020","journal-title":"Nanoscale"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"29579","DOI":"10.1021\/acsami.9b09671","article-title":"Fenton reaction-assisted photodynamic therapy for cancer with multifunctional magnetic nanoparticles","volume":"11","author":"Hou","year":"2019","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2133","DOI":"10.1002\/adma.200802366","article-title":"Inorganic nanoparticles for MRI contrast agents","volume":"21","author":"Na","year":"2009","journal-title":"Adv. Mater."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1148\/radiology.218.1.r01ja2427","article-title":"Contrast agents for MR imaging of the liver","volume":"218","author":"Semelka","year":"2001","journal-title":"Radiology"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1039\/b510982p","article-title":"Strategies for increasing the sensitivity of gadolinium based MRI contrast agents","volume":"35","author":"Caravan","year":"2006","journal-title":"Chem. Soc. Rev."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1016\/j.rcl.2009.06.006","article-title":"Involvement of gadolinium chelates in the mechanism of nephrogenic systemic fibrosis: An update","volume":"47","author":"Port","year":"2009","journal-title":"Radiol. Clin."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1021\/ja01539a017","article-title":"Preparation of graphitic oxide","volume":"80","author":"Hummers","year":"1958","journal-title":"J. Am. Chem. Soc."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4236\/graphene.2017.61001","article-title":"Synthesis of graphene oxide (GO) by modified hummers method and its thermal reduction to obtain reduced graphene oxide (rGO)","volume":"6","author":"Alam","year":"2017","journal-title":"Graphene"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/23\/15087\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:31:56Z","timestamp":1760146316000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/23\/15087"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,1]]},"references-count":60,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["ijms232315087"],"URL":"https:\/\/doi.org\/10.3390\/ijms232315087","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,1]]}}}