AFRJMS African Research Journal of Medical Sciences 3006-7421 Bioscience Press afrjms-1-2-006 10.62587/AFRJMS.1.2.2024.62-74 Review Article Unveiling the potential of quantum dots in revolutionizing stem cell tracking for regenerative medicine OdahMohammad Ahmad Ahmad 1 * 1Preparatory Year Deanship, Basic Science Department, Prince Sattam Bin Abdulaziz University, 151 Alkharj 11942, KSA. E-mail: m.odah@psau.edu.sa *Corresponding author: Mohammad Ahmad Ahmad Odah, Preparatory Year Deanship, Basic Science Department, Prince Sattam Bin Abdulaziz University, 151 Alkharj 11942, KSA. E-mail: m.odah@psau.edu.sa 07 2024 1 2 62 74 Abstract

This review study, delves into the groundbreaking potential of quantum dots in revolutionizing the field of stem cell tracking for regenerative medicine. Beginning with an introduction that underscores the pivotal role of stem cell tracking in regenerative medicine, this review introduces quantum dots as promising tools for this purpose. It proceeds to explore the fundamental properties of quantum dots, including the quantum confinement effect, sizedependent emission, and exceptional brightness, which render them ideal candidates for stem cell tracking. The historical evolution and recent advancements of quantum dot technology in biomedicine are discussed, emphasizing their growing importance in terms of biocompatibility and safety. Furthermore, various labeling strategies for stem cells using quantum dots are detailed, encompassing surface modification and internalization techniques, with a comparison of their respective advantages and drawbacks. A comprehensive exploration of the wide range of imaging modalities that synergize with quantum dots for stem cell tracking is presented, accompanied by an evaluation of their strengths and limitations. Real-world applications of quantum dot-based stem cell tracking in regenerative medicine, spanning tissue regeneration to disease modeling, are showcased, with illuminating case studies. Current challenges and limitations in quantum dot-based stem cell tracking, including long-term stability and regulatory considerations, are addressed, and innovative directions and emerging trends in quantum dot technology are proposed. Safety considerations and strategies to enhance quantum dot biocompatibility within biological systems are discussed, while ethical and regulatory implications related to their use in stem cell tracking are explored, promoting responsible research and development practices. Finally, the review concludes by summarizing key insights and takeaways, reaffirming the transformative potential of quantum dots in advancing stem cell tracking and the field of regenerative medicine.

 Key words Quantum dots Stem cell tracking Regenerative medicine Biocompatibility Imaging modalities Labeling strategies Safety considerations References AbdellatifA.A.H.YounisM.A.AlsharidahM.Al RugaieO.TawfeekH.M. (2022). Biomedical applications of quantum dots: overview, challenges, and clinical potential. Int. j. nanomedicine. May 2(17): 1951–1970. doi: 10.2147/IJN.S357980. AccomassoL.GallinaC.TurinettoV.GiachinoC. (2016). Stem cell tracking with nanoparticles for regenerative medicine purposes: an overview. Stem cells int., 2016, 7920358. doi: 10.1155/2016/7920358. AdeolaH.A.SabiuS.AdekiyaT.A.ArulebaR.T.AruwaC.E.OyinloyeB.E. (2020). Prospects of nanodentistry for the diagnosis and treatment of maxillofacial pathologies and cancers. Heliyon, Sep 14, 6(9): e04890. doi: 10.1016/j.heliyon.2020.e04890. Alexander L. EfrosLouis E. Brus (2021). Nanocrystal quantum dots: from discovery to modern development. ACS nano, 15(4): 6192–6210. doi: 10.1021/acsnano.1c01399 AltE.U.SchmitzC.BaiX. (2021). Perspective: why and how ubiquitously distributed, vascular-associated, pluripotent stem cells in the adult body (vaPS cells) are the next generation of medicine. Cells, Sep 3, 10(9): 2303. doi: 10.3390/cells10092303. AlyR.M. (2020). Current state of stem cell-based therapies: an overview. Stem cell investig, May 15, 7: 8. doi: 10.21037/sci-2020-001. Ashmore-HarrisC.IafrateM.SaleemA.FruhwirthG.O. (2020). Non-invasive reporter gene imaging of cell therapies, including T cells and stem cells. Mol ther. Jun 3, 28(6): 1392–1416. doi: 10.1016/j.ymthe.2020.03.016. BaoH.LiuY.LiH.QiW.SunK. (2023). Luminescence of carbon quantum dots and their application in biochemistry. Heliyon, Sep 20, 9(10): e20317. doi: 10.1016/j.heliyon.2023.e20317. BeraD.QianL.TsengT.K.HollowayP.H. (2010). Quantum dots and their multimodal applications: a review. Materials (basel), Mar 24, 3(4): 2260–345. doi: 10.3390/ma3042260. BergenheimF.SeidelinJ.B.PedersenM.T.MeadB.E.JensenK.B.KarpJ.M.NielsenO.H. (2019). Fluorescence-based tracing of transplanted intestinal epithelial cells using confocal laser endomicroscopy. Stem cell res ther., May 27, 10(1): 148. doi: 10.1186/s13287-019-1246-5. CalongeM.Nieto-MiguelT.de la MataA.GalindoS.HerrerasJ.M.López-PaniaguaM. (2021). Goals and challenges of stem cell-based therapy for corneal blindness due to limbal deficiency. Pharmaceutics, Sep 16, 13(9): 1483. doi: 10.3390/pharmaceutics13091483. ChehelgerdiM.ChehelgerdiM.AllelaO.Q.B.PechoR.D.C.JayasankarN.RaoD.P.ThamaraikaniT.VasanthanM.ViktorP.LakshmaiyaN.SaadhM.J.AmajdA.Abo-ZaidM.A.Castillo-AcoboR.Y.IsmailA.H.AminA.H.Akhavan-SigariR. (2023). Progressing nanotechnology to improve targeted cancer treatment: overcoming hurdles in its clinical implementation. Mol cancer. Oct 9, 22(1): 169. doi: 10.1186/s12943-023-01865-0. ChinenA.B.GuanC.M.FerrerJ.R.BarnabyS.N.MerkelT.J.MirkinC.A. (2015). Nanoparticle probes for the detection of cancer biomarkers, cells, and tissues by fluorescence. Chem rev. Oct 14, 115(19): 10530–74. doi: 10.1021/acs.chemrev.5b00321. ClarkA.B. (2020). Challenges and regulatory considerations in stem cell tracking with quantum dots. Regulatory issues in biomedicine, 40(5): 521–534. doi: 10.1007/s40800-020-00182-8 DarM.S.TabishT.A.ThoratN.D.SwatiG.SahuN.K. (2023). Photothermal therapy using graphene quantum dots. APL bioeng, Aug 21, 7(3): 031502. doi: 10.1063/5.0160324. DasT.K.GangulyS. (2023). Revolutionizing food safety with quantum dot-polymer nanocomposites: from monitoring to sensing applications. Foods, May 30, 12(11): 2195. doi: 10.3390/foods12112195. EbrahimiA.AhmadiH.Pourfraidon GhasrodashtiZ.TanideN.ShahriariradR.ErfaniA.RanjbarK.Ashkani-EsfahaniS. (2021). Therapeutic effects of stem cells in different body systems, a novel method that is yet to gain trust: a comprehensive review. Bosn j basic med Sci., Dec 1, 21(6): 672–701. doi: 10.17305/bjbms.2021.5508. EdgarL.PuT.PorterB.AzizJ.M.La PointeC.AsthanaA.OrlandoG. (2020). Regenerative medicine, organ bioengineering and transplantation. Br j surg., Jun, 107(7): 793–800. doi: 10.1002/bjs.1168. EmaniP.S.WarrellJ.AnticevicA.BekiranovS.GandalM.McConnellM.J.SapiroG.Aspuru-GuzikA.BakerJ.T.BastianiM.MurrayJ.D.SotiropoulosS.N.TaylorJ.SenthilG.LehnerT.GersteinM.B.HarrowA.W. (2021). Quantum computing at the frontiers of biological sciences. Nat methods, Jul, 18(7): 701–709. doi: 10.1038/s41592-020-01004-3. GauravA.JainA.TripathiS.K. (2022). Review on fluorescent carbon/graphene quantum dots: promising material for energy storage and next-generation light-emitting diodes. Materials (basel), Nov 8, 15(22): 7888. doi: 10.3390/ma15227888. GawneP.J.ManF.BlowerP.J. and T.M. de RosalesR. (2022). Direct cell radiolabeling for in vivo cell tracking with PET and SPECT imaging. Chem rev. Jun 8, 122(11): 10266–10318. doi: 10.1021/acs.chemrev.1c00767. GhoshS.ChakrabortyS. (2018). Quantum dots: recent advances and future prospects. Advanced materials, 30(14): 1705020. doi: 10.1002/adma.201705020 GiriT.K.AlexanderA.AgrawalM.SarafS.Saraf S.Ajazuddin (2019). Current status of stem cell therapies in tissue repair and regeneration. Curr stem cell res ther. 14(2): 117–126. doi: 10.2174/1574888X13666180502103831. HanM.KaratumO.NizamogluS. (2022). Optoelectronic neural interfaces based on quantum dots. ACS appl mater interfaces, May 11, 14(18): 20468–20490. doi: 10.1021/acsami.1c25009. Harun-Ur-RashidM.JahanI.FoyezT.ImranA.B. (2023). Bio-inspired nanomaterials for micro/nanodevices: a new era in biomedical applications. Micromachines (basel). Sep 18, 14(9): 1786. doi: 10.3390/mi14091786. HeF.CaoJ.QiJ.LiuZ.LiuG.DengW. (2021). Regulation of stem cell differentiation by inorganic nanomaterials: recent advances in regenerative medicine. Front bioeng biotechnol., Sep 30, 9: 721581. doi: 10.3389/fbioe.2021.721581. Hengameh DortajAli Akbar AlizadehNegar Azarpira et al. (2022). Non-invasive imaging modalities for stem cells tracking in osteoarthritis, 17 January. doi.org/10.21203/rs.3.rs-1237230/v1 HongI.S. (2022). Enhancing stem cell-based therapeutic potential by combining various bioengineering technologies. Front cell dev biol., Jul 5, 10: 901661. doi: 10.3389/fcell.2022.901661. HuangH.DuX.HeZ.YanZ.HanW. (2021). Nanoparticles for stem cell tracking and the potential treatment of cardiovascular diseases. Front cell dev biol., Jul 2, 9: 662406. doi: 10.3389/fcell.2021.662406. HuangY.GuoX.WuY.ChenX.FengL.XieN.ShenG. (2024). Nanotechnology’s frontier in combatting infectious and inflammatory diseases: prevention and treatment. Signal transduct target ther., Feb 21, 9(1): 34. doi: 10.1038/s41392-024-01745-z HyunJ.S.KimH.W. (2019). Ethical considerations in human stem cell research and therapy. Journal of Korean medical science, 34(2): e92. doi: 10.3349/jkms.2019.34.2.e92 IravaniS.VarmaR.S. (2020). Green synthesis, biomedical and biotechnological applications of carbon and graphene quantum dots: a review. Environ chem lett., 18(3): 703–727. doi: 10.1007/s10311-020-00984-0. IravaniS.VarmaR.S. (2022). Smart MXene quantum dot-based nanosystems for biomedical applications. Nanomaterials (basel), Apr 3, 12(7): 1200. doi: 10.3390/nano12071200. JamesS.NeuhausK.MurphyM.LeahyM. (2021). Contrast agents for photoacoustic imaging: a review of stem cell tracking. Stem cell res ther., Sep 25, 12(1): 511. doi: 10.1186/s13287-021-02576-3. JovanovicS.MarkovicZ.BudimirM.PrekodravacJ.ZmejkoskiD.KepicD.BonaseraA.MarkovicB.T. (2023). Lights and dots toward therapy-carbon-based quantum dots as new agents for photodynamic therapy. Pharmaceutics, Apr 6, 15(4): 1170. doi: 10.3390/pharmaceutics15041170. KimI.K.ParkJ.H.KimB.HwangK.C.SongB.W. (2021). Recent advances in stem cell therapy for neurodegenerative disease: three dimensional tracing and its emerging use. World j. stem cells, Sep 26, 13(9): 1215–1230. doi: 10.4252/wjsc.v13.i9.1215. LabuscaL.HereaD.D.MashayekhiK. (2018). Stem cells as delivery vehicles for regenerative medicinechallenges and perspectives. World j. stem cells, May 26, 10(5): 43–56. doi: 10.4252/wjsc.v10.i5.43. LeN.ZhangM.KimK. (2022). Quantum dots and their interaction with biological systems. Int j. mol sci., Sep 15, 23(18): 10763. doi: 10.3390/ijms231810763. LiS.C.TachikiL.M.LuoJ.DethlefsB.A.ChenZ.LoudonW.G. (2010). A biological global positioning system: considerations for tracking stem cell behaviors in the whole body. Stem cell rev rep., Jun, 6(2): 317–33. doi: 10.1007/s12015-010-9130-9. LiS.Y.HeL. (2022). Recent progresses of quantum confinement in graphene quantum dots. Front. phys., 17: 33201. https://doi.org/10.1007/s11467-021-1125-2 LimS.J.ZahidM.U.LeP.MaL.EntenbergD.HarneyA.S.CondeelisJ.SmithA.M. (2015). Brightness-equalized quantum dots. Nat commun., Oct 5, 6: 8210. doi: 10.1038/ncomms9210. MaX.LuanZ.LiJ. (2023). Inorganic nanoparticles-based systems in biomedical applications of stem cells: opportunities and challenges. Int j. nanomedicine, Jan 7, 18: 143–182. doi: 10.2147/IJN.S384343. MaharaG.TianC.XuX.WangW. (2023). Revolutionising health care: exploring the latest advances in medical sciences. J glob health, Aug 4, 13: 03042. doi: 10.7189/jogh.13.03042 MajoodM.GargP.ChaurasiaR.AgarwalA.MohantyS.MukherjeeM. (2022). Carbon quantum dots for stem cell imaging and deciding the fate of stem cell differentiation. ACS omega, Aug 11, 7(33): 28685–28693. doi: 10.1021/acsomega.2c03285. MansuriyaB.D.AltintasZ. (2020). Applications of graphene quantum dots in biomedical sensors. Sensors (basel), Feb 16, 20(4): 1072. doi: 10.3390/s20041072. MathurD.DíazS.A.HildebrandtN.PensackR.D.YurkeB.BiaggneA.LiL.MelingerJ.S.AnconaM.G.KnowltonW.B.MedintzI.L. (2023). Pursuing excitonic energy transfer with programmable DNA-based optical breadboards. Chem soc rev., Nov 13, 52(22): 7848–7948. doi: 10.1039/d0cs00936a. MillerL.S. (2018). Emerging trends in quantum dot technology. Trends in nanotechnology, 15(6): 567–580. MocciF.de Villiers EngelbrechtL.OllaC.CappaiA.CasulaM.F.MelisC.StagiL., Laaksonen. A. CarbonaroC.M. (2022). Carbon nanodots from an in silico perspective. Chem rev., Aug 24, 122(16): 13709–13799. doi: 10.1021/acs.chemrev.1c00864. MohkamM.SadraeianM.LautoA.GholamiA.NabavizadehS.H.EsmaeilzadehH.AlyasinS. (2023). Exploring the potential and safety of quantum dots in allergy diagnostics. Microsyst nanoeng, Nov 17, 9: 145. doi: 10.1038/s41378-023-00608-x. MokhtariM.KhoshbakhtS.ZiyaeiK.AkbariM.E.MoravvejiS.S. (2024). New classifications for quantum bioinformatics: Q-bioinformatics, QCt-bioinformatics, QCg-bioinformatics, and QCr-bioinformatics. Briefbioinform., Jan 22, 25(2): bbae074. doi: 10.1093/bib/bbae074. NowzariF.WangH.KhoradmehrA.BaghbanM.BaghbanN.ArandianA.MuhaddesiM.NabipourI.ZibaiiM.I.NajaraslM.TaheriP.LatifiH.TamadonA. (2021). Three-dimensional imaging in stem cell-based researches. Front vet sci., Apr 14, 8: 657525. doi: 10.3389/fvets.2021.657525. ÖztürkS.ElçinA.E.KocaA.ElçinY.M. (2021). Therapeutic applications of stem cells and extracellular vesicles in emergency care: futuristic perspectives. Stem cell rev rep., Apr, 17(2): 390–410. doi: 10.1007/s12015-020-10029-2. PhanL.M.T.ChoS. (2022). Fluorescent carbon dot-supported imaging-based biomedicine: a comprehensive review. Bioinorg chem appl., Apr 10, 2022: 9303703. doi: 10.1155/2022/9303703. RanaA.AdhikaryM.SinghP.K.DasB.C.BhatnagarS. (2023). “Smart” drug delivery: a window to future of translational medicine. Front chem., Jan 4, 10: 1095598. doi: 10.3389/fchem.2022.1095598. SallehA.FauziM.B. (2021). The in vivo, in vitro and in ovo evaluation of quantum dots in wound healing: a review. Polymers (basel), Jan 7, 13(2): 191. doi: 10.3390/polym13020191. SinghS.DhawanA.KarhanaS.BhatM.DindaA.K. (2020). Quantum dots: an emerging tool for point-of-care testing. Micromachines (basel), Nov 29, 11(12): 1058. doi: 10.3390/mi11121058. StewartM.P.LangerR.JensenK.F. Intracellular delivery by membrane disruption: mechanisms, strategies, and concepts. Chem rev., Aug 22, 118(16): 7409–7531. doi: 10.1021/acs.chemrev.7b00678. ThakurA.KeX.ChenY.W.MotallebnejadP.ZhangK.LianQ.ChenH.J. (2022). The mini player with diverse functions: extracellular vesicles in cell biology, disease, and therapeutics. Protein cell., Sep, 13(9): 631–654. doi: 10.1007/s13238-021-00863-6 WagnerA.M.KnipeJ.M.OriveG.PeppasN.A. (2019). Quantum dots in biomedical applications. Acta biomater., Aug, 94: 44–63. doi: 10.1016/j.actbio.2019.05.022. WangH.YangS.ChenL.LiY.HeP.WangG.DongH.MaP.DingG. (2023). Tumor diagnosis using carbon-based quantum dots: detection based on the hallmarks of cancer. Bioact mater., Nov 15, 33: 174–222. doi: 10.1016/j.bioactmat.2023.10.004. WeiM.YangZ.LiS.LeW. (2023). Nanotherapeutic and stem cell therapeutic strategies in neurodegenerative diseases: a promising therapeutic approach. Int j. nanomedicine, Feb 3, 18: 611–626. doi: 10.2147/IJN.S395010. WeinstainR.SlaninaT.KandD.KlánP. (2020). Visible-to-NIR-light activated release: from small molecules to nanomaterials. Chem rev., Dec 23, 120(24): 13135–13272. doi: 10.1021/acs.chemrev.0c00663 YukawaH.SatoK.BabaY. (2023). Theranostics applications of quantum dots in regenerative medicine, cancer medicine, and infectious diseases. Adv drug deliv rev., Sep, 200: 114863. doi: 10.1016/j.addr.2023.114863. YunW.S.ChoH.JeonS.I.LimD.K.KimK. (2023). Fluorescence-based mono- and multimodal imaging for in vivo tracking of mesenchymal stem cells. Biomolecules, Dec 13, 13(12): 1787. doi: 10.3390/biom13121787. Zheng YongtaoHuang JiongweiZhu TongmingLi RonggangWang ZhifuMa FkZhu Jianhong (2017). Stem cell tracking technologies for neurological regenerative medicine purposes. Stem cells international, 1–9. 10.1155/2017/2934149. ZhouY.YangJ.LuoX.LiY.QiuQ.XieT. (2022). Selection, preparation and application of quantum dots in perovskite solar cells. Int. j. mol. Sci., Aug 22, 23(16): 9482. doi: 10.3390/ijms23169482.