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Engineered iron oxide nanoparticles to improve regenerative effects of mesenchymal stem cells

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Abstract

Mesenchymal stem cells (MSCs) based therapies are a major field of regenerative medicine. However, the success of MSC therapy relies on the efficiency of its delivery and retention, differentiation, and secreting paracrine factors at the target sites. Recent studies show that superparamagnetic iron oxide nanoparticles (SPIONs) modulate the regenerative effects of MSCs. After interacting with the cell membrane of MSCs, SPIONs can enter the cells via the endocytic pathway. The physicochemical properties of nanoparticles, including size, surface charge (zeta-potential), and surface ligand, influence their interactions with MSC, such as cellular uptake, cytotoxicity, homing factors, and regenerative related factors (VEGF, TGF-β1). Therefore, in-depth knowledge of the physicochemical properties of SPIONs might be a promising lead in regenerative and anti-inflammation research using SPIONs mediated MSCs. In this review, recent research on SPIONs with MSCs and the various designs of SPIONs are examined and summarized.

Graphic abstract

A graphical abstract describes important parameters in the design of superparamagnetic iron oxide nanoparticles, affecting mesenchymal stem cells. These physicochemical properties are closely related to the mesenchymal stem cells to achieve improved cellular responses such as homing factors and cell uptake.

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Fig. 1

(Reprinted with from Andreas et al. [47]. Copyright (2012), with permission from Elsevier)

Fig. 2

(Reprinted with from Yun et al. [26])

Fig. 3

(Reprinted with permission from Kim et al. [64]. Copyright 2018 American Chemical Society)

Fig. 4

(Reprinted with permission from Pan et al. [77]. Copyright 2007 with permission from John Wiley and Sons)

Fig. 5

(Reprinted with from Wei et al. [87]

Fig. 6

(Reprinted with permission from Jiang et al. [102]. Copyright (2010) American Chemical Society)

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References

  1. Peran M, Garcia MA, Lopez-Ruiz E, Bustamante M, Jimenez G, Madeddu R, Marchal JA. Functionalized nanostructures with application in regenerative medicine. Int J Mol Sci. 2012;13:3847–86. https://doi.org/10.3390/ijms13033847.

    Article  Google Scholar 

  2. Lowe B, Nam SY. Synthesis and biocompatibility assessment of a cysteine-based nanocomposite for applications in bone tissue engineering. Biomed Eng Lett. 2016;6:271–5. https://doi.org/10.1007/s13534-016-0239-x.

    Article  Google Scholar 

  3. Kim M, Gweon B, Koh U, Cho Y, Shin DW, Noh M, Shin JH. Matrix stiffness induces epithelial mesenchymal transition phenotypes of human epidermal keratinocytes on collagen coated two dimensional cell culture. Biomed Eng Lett. 2015;5:194–202. https://doi.org/10.1007/s13534-015-0202-2.

    Article  Google Scholar 

  4. Friedenstein AJ, Chailakhyan RK, Latsinik NV, Panasyuk AF, Keiliss-Borok IV. Stromal cells responsible for transferring the microenvironment of the hemopoietic tissues. Cloning in vitro and retransplantation in vivo. Transplantation. 1974;17:331–40. https://doi.org/10.1097/00007890-197404000-00001.

    Article  Google Scholar 

  5. Krampera M, Pizzolo G, Aprili G, Franchini M. Mesenchymal stem cells for bone, cartilage, tendon and skeletal muscle repair. Bone. 2006;39:678–83. https://doi.org/10.1016/j.bone.2006.04.020.

    Article  Google Scholar 

  6. Rahaman MN, Mao JJ. Stem cell-based composite tissue constructs for regenerative medicine. Biotechnol Bioeng. 2005;91:261–84. https://doi.org/10.1002/bit.20292.

    Article  Google Scholar 

  7. Polak JM, Bishop AE. Stem cells and tissue engineering: past, present, and future. Ann N Y Acad Sci. 2006;1068:352–66. https://doi.org/10.1196/annals.1346.001.

    Article  Google Scholar 

  8. Raghunath J, Salacinski HJ, Sales KM, Butler PE, Seifalian AM. Advancing cartilage tissue engineering: the application of stem cell technology. Curr Opin Biotechnol. 2005;16:503–9. https://doi.org/10.1016/j.copbio.2005.08.004.

    Article  Google Scholar 

  9. Spees JL, Lee RH, Gregory CA. Mechanisms of mesenchymal stem/stromal cell function. Stem Cell Res Ther. 2016;7:125. https://doi.org/10.1186/s13287-016-0363-7.

    Article  Google Scholar 

  10. Cruz FF, Weiss DJ, Rocco PR. Prospects and progress in cell therapy for acute respiratory distress syndrome. Expert Opin Biol Ther. 2016;16:1353–60. https://doi.org/10.1080/14712598.2016.1218845.

    Article  Google Scholar 

  11. Danchuk S, Ylostalo JH, Hossain F, Sorge R, Ramsey A, Bonvillain RW, Lasky JA, Bunnell BA, Welsh DA, Prockop DJ. Human multipotent stromal cells attenuate lipopolysaccharide-induced acute lung injury in mice via secretion of tumor necrosis factor-α-induced protein 6. Stem Cell Res Ther. 2011;2:27.

    Article  Google Scholar 

  12. Newman RE, Yoo D, LeRoux MA, Danilkovitch-Miagkova A. Treatment of inflammatory diseases with mesenchymal stem cells. Inflamm Allergy Drug Targets. 2009;8:110–23. https://doi.org/10.2174/187152809788462635.

    Article  Google Scholar 

  13. Di Nicola M, Carlo-Stella C, Magni M, Milanesi M, Longoni PD, Matteucci P, Grisanti S, Gianni AM. Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood. 2002;99:3838–43. https://doi.org/10.1182/blood.v99.10.3838.

    Article  Google Scholar 

  14. Heathman TR, Nienow AW, McCall MJ, Coopman K, Kara B, Hewitt CJ. The translation of cell-based therapies: clinical landscape and manufacturing challenges. Regen Med. 2015;10:49–64. https://doi.org/10.2217/rme.14.73.

    Article  Google Scholar 

  15. Kang SK, Shin IS, Ko MS, Jo JY, Ra JC. Journey of mesenchymal stem cells for homing: strategies to enhance efficacy and safety of stem cell therapy. Stem Cells Int. 2012;2012:342968. https://doi.org/10.1155/2012/342968.

    Article  Google Scholar 

  16. Wynn RF, Hart CA, Corradi-Perini C, O’Neill L, Evans CA, Wraith JE, Fairbairn LJ, Bellantuono I. A small proportion of mesenchymal stem cells strongly expresses functionally active CXCR4 receptor capable of promoting migration to bone marrow. Blood. 2004;104:2643–5. https://doi.org/10.1182/blood-2004-02-0526.

    Article  Google Scholar 

  17. Fan H, Zhao G, Liu L, Liu F, Gong W, Liu X, Yang L, Wang J, Hou Y. Pre-treatment with IL-1β enhances the efficacy of MSC transplantation in DSS-induced colitis. Cell Mol Immunol. 2012;9:473.

    Article  Google Scholar 

  18. Ponte AL, Marais E, Gallay N, Langonne A, Delorme B, Herault O, Charbord P, Domenech J. The in vitro migration capacity of human bone marrow mesenchymal stem cells: comparison of chemokine and growth factor chemotactic activities. Stem Cells. 2007;25:1737–45. https://doi.org/10.1634/stemcells.2007-0054.

    Article  Google Scholar 

  19. Hung SC, Pochampally RR, Hsu SC, Sanchez C, Chen SC, Spees J, Prockop DJ. Short-term exposure of multipotent stromal cells to low oxygen increases their expression of CX3CR1 and CXCR4 and their engraftment in vivo. PLoS ONE. 2007;2:e416. https://doi.org/10.1371/journal.pone.0000416.

    Article  Google Scholar 

  20. Jing XH, Yang L, Duan XJ, Xie B, Chen W, Li Z, Tan HB. In vivo MR imaging tracking of magnetic iron oxide nanoparticle labeled, engineered, autologous bone marrow mesenchymal stem cells following intra-articular injection. Joint Bone Spine. 2008;75:432–8. https://doi.org/10.1016/j.jbspin.2007.09.013.

    Article  Google Scholar 

  21. Niemeyer M, Oostendorp RA, Kremer M, Hippauf S, Jacobs VR, Baurecht H, Ludwig G, Piontek G, Bekker-Ruz V, Timmer S, et al. Non-invasive tracking of human haemopoietic CD34(+) stem cells in vivo in immunodeficient mice by using magnetic resonance imaging. Eur Radiol. 2010;20:2184–93. https://doi.org/10.1007/s00330-010-1773-z.

    Article  Google Scholar 

  22. Wilhelm C, Bal L, Smirnov P, Galy-Fauroux I, Clement O, Gazeau F, Emmerich J. Magnetic control of vascular network formation with magnetically labeled endothelial progenitor cells. Biomaterials. 2007;28:3797–806. https://doi.org/10.1016/j.biomaterials.2007.04.047.

    Article  Google Scholar 

  23. Phanapavudhikul P, Shen S, Ng WK, Tan RB. Formulation of Fe3O4/acrylate co-polymer nanocomposites as potential drug carriers. Drug Deliv. 2008;15:177–83. https://doi.org/10.1080/10717540801952597.

    Article  Google Scholar 

  24. Sakhtianchi R, Minchin RF, Lee KB, Alkilany AM, Serpooshan V, Mahmoudi M. Exocytosis of nanoparticles from cells: role in cellular retention and toxicity. Adv Colloid Interface Sci. 2013;201–202:18–29. https://doi.org/10.1016/j.cis.2013.10.013.

    Article  Google Scholar 

  25. Anzai Y, Piccoli CW, Outwater EK, Stanford W, Bluemke DA, Nurenberg P, Saini S, Maravilla KR, Feldman DE, Schmiedl UP, et al. Evaluation of neck and body metastases to nodes with ferumoxtran 10-enhanced MR imaging: phase III safety and efficacy study. Radiology. 2003;228:777–88. https://doi.org/10.1148/radiol.2283020872.

    Article  Google Scholar 

  26. Yun WS, Choi JS, Ju HM, Kim MH, Choi SJ, Oh ES, Seo YJ, Key J. Enhanced homing technique of mesenchymal stem cells using iron oxide nanoparticles by magnetic attraction in olfactory-injured mouse models. Int J Mol Sci. 2018;19:1376. https://doi.org/10.3390/ijms19051376.

    Article  Google Scholar 

  27. Fayol D, Frasca G, Le Visage C, Gazeau F, Luciani N, Wilhelm C. Use of magnetic forces to promote stem cell aggregation during differentiation, and cartilage tissue modeling. Adv Mater. 2013;25:2611–6. https://doi.org/10.1002/adma.201300342.

    Article  Google Scholar 

  28. Yamamoto Y, Ito A, Fujita H, Nagamori E, Kawabe Y, Kamihira M. Functional evaluation of artificial skeletal muscle tissue constructs fabricated by a magnetic force-based tissue engineering technique. Tissue Eng Part A. 2011;17:107–14. https://doi.org/10.1089/ten.TEA.2010.0312.

    Article  Google Scholar 

  29. Souza GR, Molina JR, Raphael RM, Ozawa MG, Stark DJ, Levin CS, Bronk LF, Ananta JS, Mandelin J, Georgescu MM, et al. Three-dimensional tissue culture based on magnetic cell levitation. Nat Nanotechnol. 2010;5:291–6. https://doi.org/10.1038/nnano.2010.23.

    Article  Google Scholar 

  30. Chaudeurge A, Wilhelm C, Chen-Tournoux A, Farahmand P, Bellamy V, Autret G, Ménager C, Hagège A, Larghéro J, Gazeau F. Can magnetic targeting of magnetically labeled circulating cells optimize intramyocardial cell retention? Cell Transplant. 2012;21:679–91.

    Article  Google Scholar 

  31. Ahn YJ, Kong TH, Choi JS, Yun WS, Key J, Seo YJ. Strategies to enhance efficacy of SPION-labeled stem cell homing by magnetic attraction: a systemic review with meta-analysis. Int J Nanomed. 2019;14:4849–66. https://doi.org/10.2147/IJN.S204910.

    Article  Google Scholar 

  32. Nel A, Xia T, Madler L, Li N. Toxic potential of materials at the nanolevel. Science. 2006;311:622–7. https://doi.org/10.1126/science.1114397.

    Article  Google Scholar 

  33. Mojica Pisciotti ML, Lima E Jr, Vasquez Mansilla M, Tognoli VE, Troiani HE, Pasa AA, Creczynski-Pasa TB, Silva AH, Gurman P, Colombo L, et al. In vitro and in vivo experiments with iron oxide nanoparticles functionalized with DEXTRAN or polyethylene glycol for medical applications: magnetic targeting. J Biomed Mater Res B Appl Biomater. 2014;102:860–8. https://doi.org/10.1002/jbm.b.33068.

    Article  Google Scholar 

  34. Buyukhatipoglu K, Clyne AM. Superparamagnetic iron oxide nanoparticles change endothelial cell morphology and mechanics via reactive oxygen species formation. J Biomed Mater Res A. 2011;96:186–95. https://doi.org/10.1002/jbm.a.32972.

    Article  Google Scholar 

  35. Soenen SJ, Nuytten N, De Meyer SF, De Smedt SC, De Cuyper M. High intracellular iron oxide nanoparticle concentrations affect cellular cytoskeleton and focal adhesion kinase-mediated signaling. Small. 2010;6:832–42. https://doi.org/10.1002/smll.200902084.

    Article  Google Scholar 

  36. Soenen SJ, Himmelreich U, Nuytten N, Pisanic TR, 2nd, Ferrari A, De Cuyper M. Intracellular nanoparticle coating stability determines nanoparticle diagnostics efficacy and cell functionality. Small 2010; 6:2136–2145. https://doi.org/10.1002/smll.201000763.

  37. Fayol D, Luciani N, Lartigue L, Gazeau F, Wilhelm C. Managing magnetic nanoparticle aggregation and cellular uptake: a precondition for efficient stem-cell differentiation and MRI tracking. Adv Healthc Mater. 2013;2:313–25. https://doi.org/10.1002/adhm.201200294.

    Article  Google Scholar 

  38. Chang YK, Liu YP, Ho JH, Hsu SC, Lee OK. Amine-surface-modified superparamagnetic iron oxide nanoparticles interfere with differentiation of human mesenchymal stem cells. J Orthop Res. 2012;30:1499–506.

    Article  Google Scholar 

  39. Huang X, Zhang F, Wang Y, Sun X, Choi KY, Liu D, Choi JS, Shin TH, Cheon J, Niu G, et al. Design considerations of iron-based nanoclusters for noninvasive tracking of mesenchymal stem cell homing. ACS Nano. 2014;8:4403–14. https://doi.org/10.1021/nn4062726.

    Article  Google Scholar 

  40. Yun S, Shin TH, Lee JH, Cho MH, Kim IS, Kim JW, Jung K, Lee IS, Cheon J, Park KI. Design of magnetically labeled cells (mag-cells) for in vivo control of stem cell migration and differentiation. Nano Lett. 2018;18:838–45. https://doi.org/10.1021/acs.nanolett.7b04089.

    Article  Google Scholar 

  41. Han J, Kim B, Shin J-Y, Ryu S, Noh M, Woo J, Park J-S, Lee Y, Lee N, Hyeon T. Iron oxide nanoparticle-mediated development of cellular gap junction crosstalk to improve mesenchymal stem cells’ therapeutic efficacy for myocardial infarction. ACS Nano. 2015;9:2805–19.

    Article  Google Scholar 

  42. Schafer R. Labeling and imaging of stem cells—promises and concerns. Transfus Med Hemother. 2010;37:85–9. https://doi.org/10.1159/000287271.

    Article  Google Scholar 

  43. Zheng Y, Huang J, Zhu T, Li R, Wang Z, Ma F, Zhu J. Stem cell tracking technologies for neurological regenerative medicine purposes. Stem Cells Int. 2017;2017:2934149. https://doi.org/10.1155/2017/2934149.

    Article  Google Scholar 

  44. Santra S, Kaittanis C, Grimm J, Perez JM. Drug/dye-loaded, multifunctional iron oxide nanoparticles for combined targeted cancer therapy and dual optical/magnetic resonance imaging. Small. 2009;5:1862–8. https://doi.org/10.1002/smll.200900389.

    Article  Google Scholar 

  45. Jasmin, Torres AL, Jelicks L, de Carvalho AC, Spray DC, Mendez-Otero R. Labeling stem cells with superparamagnetic iron oxide nanoparticles: analysis of the labeling efficacy by microscopy and magnetic resonance imaging. Methods Mol Biol. 2012;906:239–52. https://doi.org/10.1007/978-1-61779-953-2_18.

    Article  Google Scholar 

  46. Vanecek V, Zablotskii V, Forostyak S, Ruzicka J, Herynek V, Babic M, Jendelova P, Kubinova S, Dejneka A, Sykova E. Highly efficient magnetic targeting of mesenchymal stem cells in spinal cord injury. Int J Nanomed. 2012;7:3719–30. https://doi.org/10.2147/IJN.S32824.

    Article  Google Scholar 

  47. Andreas K, Georgieva R, Ladwig M, Mueller S, Notter M, Sittinger M, Ringe J. Highly efficient magnetic stem cell labeling with citrate-coated superparamagnetic iron oxide nanoparticles for MRI tracking. Biomaterials. 2012;33:4515–25. https://doi.org/10.1016/j.biomaterials.2012.02.064.

    Article  Google Scholar 

  48. Hu SL, Lu PG, Zhang LJ, Li F, Chen Z, Wu N, Meng H, Lin JK, Feng H. In vivo magnetic resonance imaging tracking of SPIO-labeled human umbilical cord mesenchymal stem cells. J Cell Biochem. 2012;113:1005–12. https://doi.org/10.1002/jcb.23432.

    Article  Google Scholar 

  49. Mishra SK, Khushu S, Singh AK, Gangenahalli G. Homing and tracking of iron oxide labelled mesenchymal stem cells after infusion in traumatic brain injury mice: a longitudinal in vivo MRI study. Stem Cell Rev Rep. 2018;14:888–900. https://doi.org/10.1007/s12015-018-9828-7.

    Article  Google Scholar 

  50. Taboada E, Rodriguez E, Roig A, Oro J, Roch A, Muller RN. Relaxometric and magnetic characterization of ultrasmall iron oxide nanoparticles with high magnetization. Evaluation as potential T1 magnetic resonance imaging contrast agents for molecular imaging. Langmuir. 2007;23:4583–8. https://doi.org/10.1021/la063415s.

    Article  Google Scholar 

  51. Song M, Kim YJ, Kim YH, Roh J, Kim SU, Yoon BW. Using a neodymium magnet to target delivery of ferumoxide-labeled human neural stem cells in a rat model of focal cerebral ischemia. Hum Gene Ther. 2010;21:603–10. https://doi.org/10.1089/hum.2009.144.

    Article  Google Scholar 

  52. Li X, Wei Z, Lv H, Wu L, Cui Y, Yao H, Li J, Zhang H, Yang B, Jiang J. Iron oxide nanoparticles promote the migration of mesenchymal stem cells to injury sites. Int J Nanomed. 2019;14:573–89. https://doi.org/10.2147/IJN.S184920.

    Article  Google Scholar 

  53. Devine SM, Cobbs C, Jennings M, Bartholomew A, Hoffman R. Mesenchymal stem cells distribute to a wide range of tissues following systemic infusion into nonhuman primates. Blood. 2003;101:2999–3001. https://doi.org/10.1182/blood-2002-06-1830.

    Article  Google Scholar 

  54. Xu C, Miranda-Nieves D, Ankrum JA, Matthiesen ME, Phillips JA, Roes I, Wojtkiewicz GR, Juneja V, Kultima JR, Zhao W, et al. Tracking mesenchymal stem cells with iron oxide nanoparticle loaded poly(lactide-co-glycolide) microparticles. Nano Lett. 2012;12:4131–9. https://doi.org/10.1021/nl301658q.

    Article  Google Scholar 

  55. Shin TH, Cheon J. Synergism of nanomaterials with physical stimuli for biology and medicine. Acc Chem Res. 2017;50:567–72. https://doi.org/10.1021/acs.accounts.6b00559.

    Article  Google Scholar 

  56. Cores J, Caranasos TG, Cheng K. Magnetically targeted stem cell delivery for regenerative medicine. J Funct Biomater. 2015;6:526–46. https://doi.org/10.3390/jfb6030526.

    Article  Google Scholar 

  57. Frank JA, Miller BR, Arbab AS, Zywicke HA, Jordan EK, Lewis BK, Bryant LH Jr, Bulte JW. Clinically applicable labeling of mammalian and stem cells by combining superparamagnetic iron oxides and transfection agents. Radiology. 2003;228:480–7. https://doi.org/10.1148/radiol.2281020638.

    Article  Google Scholar 

  58. Lewin M, Carlesso N, Tung CH, Tang XW, Cory D, Scadden DT, Weissleder R. Tat peptide-derivatized magnetic nanoparticles allow in vivo tracking and recovery of progenitor cells. Nat Biotechnol. 2000;18:410–4. https://doi.org/10.1038/74464.

    Article  Google Scholar 

  59. Gamarra LF, Pavon LF, Marti LC, Pontuschka WM, Mamani JB, Carneiro SM, Camargo-Mathias MI, Moreira-Filho CA, Amaro E Jr. In vitro study of CD133 human stem cells labeled with superparamagnetic iron oxide nanoparticles. Nanomedicine. 2008;4:330–9. https://doi.org/10.1016/j.nano.2008.05.002.

    Article  Google Scholar 

  60. Li L, Jiang W, Luo K, Song H, Lan F, Wu Y, Gu Z. Superparamagnetic iron oxide nanoparticles as MRI contrast agents for non-invasive stem cell labeling and tracking. Theranostics. 2013;3:595–615. https://doi.org/10.7150/thno.5366.

    Article  Google Scholar 

  61. Park J, An K, Hwang Y, Park JG, Noh HJ, Kim JY, Park JH, Hwang NM, Hyeon T. Ultra-large-scale syntheses of monodisperse nanocrystals. Nat Mater. 2004;3:891–5. https://doi.org/10.1038/nmat1251.

    Article  Google Scholar 

  62. Li X, Wei Z, Li B, Li J, Lv H, Wu L, Zhang H, Yang B, Zhu M, Jiang J. In vivo migration of Fe3O4@ polydopamine nanoparticle-labeled mesenchymal stem cells to burn injury sites and their therapeutic effects in a rat model. Biomaterials science. 2019;7:2861–72. https://doi.org/10.1039/C9BM00242A

    Article  Google Scholar 

  63. Duan X, Li Y. Physicochemical characteristics of nanoparticles affect circulation, biodistribution, cellular internalization, and trafficking. Small. 2013;9:1521–32. https://doi.org/10.1002/smll.201201390.

    Article  Google Scholar 

  64. Kim HY, Kumar H, Jo MJ, Kim J, Yoon JK, Lee JR, Kang M, Choo YW, Song SY, Kwon SP, et al. Therapeutic efficacy-potentiated and diseased organ-targeting nanovesicles derived from mesenchymal stem cells for spinal cord injury treatment. Nano Lett. 2018;18:4965–75. https://doi.org/10.1021/acs.nanolett.8b01816.

    Article  Google Scholar 

  65. Chung TH, Hsu SC, Wu SH, Hsiao JK, Lin CP, Yao M, Huang DM. Dextran-coated iron oxide nanoparticle-improved therapeutic effects of human mesenchymal stem cells in a mouse model of Parkinson’s disease. Nanoscale. 2018;10:2998–3007. https://doi.org/10.1039/c7nr06976f.

    Article  Google Scholar 

  66. Hillaireau H, Couvreur P. Nanocarriers’ entry into the cell: relevance to drug delivery. Cell Mol Life Sci. 2009;66:2873–96.

    Article  Google Scholar 

  67. Zhang S, Gao H, Bao G. Physical principles of nanoparticle cellular endocytosis. ACS Nano. 2015;9:8655–71. https://doi.org/10.1021/acsnano.5b03184.

    Article  Google Scholar 

  68. Shang L, Nienhaus K, Nienhaus GU. Engineered nanoparticles interacting with cells: size matters. J Nanobiotechnology. 2014;12:5. https://doi.org/10.1186/1477-3155-12-5.

    Article  Google Scholar 

  69. Jiang W, Kim BYS, Rutka JT, Chan WCW. Nanoparticle-mediated cellular response is size-dependent. Nat Nanotechnol. 2008;3:145–50. https://doi.org/10.1038/nnano.2008.30.

    Article  Google Scholar 

  70. Wang T, Wang L, Li X, Hu X, Han Y, Luo Y, Wang Z, Li Q, Aldalbahi A, Wang L, et al. Size-dependent regulation of intracellular trafficking of polystyrene nanoparticle-based drug-delivery systems. ACS Appl Mater Interfaces. 2017;9:18619–25. https://doi.org/10.1021/acsami.7b05383.

    Article  Google Scholar 

  71. Oh N, Park JH. Endocytosis and exocytosis of nanoparticles in mammalian cells. Int J Nanomed. 2014;9(Suppl 1):51–63. https://doi.org/10.2147/IJN.S26592.

    Article  Google Scholar 

  72. Copolovici DM, Langel K, Eriste E, Langel U. Cell-penetrating peptides: design, synthesis, and applications. ACS Nano. 2014;8:1972–94. https://doi.org/10.1021/nn4057269.

    Article  Google Scholar 

  73. Kou L, Sun J, Zhai Y, He Z. The endocytosis and intracellular fate of nanomedicines: implication for rational design. Asian J Pharm Sci. 2013;8:1–10.

    Article  Google Scholar 

  74. Rejman J, Oberle V, Zuhorn IS, Hoekstra D. Size-dependent internalization of particles via the pathways of clathrin-and caveolae-mediated endocytosis. Biochem J. 2004;377:159–69. https://doi.org/10.1042/Bj20031253.

    Article  Google Scholar 

  75. Shang L, Nienhaus K, Jiang X, Yang L, Landfester K, Mailander V, Simmet T, Nienhaus GU. Nanoparticle interactions with live cells: quantitative fluorescence microscopy of nanoparticle size effects. Beilstein J Nanotechnol. 2014;5:2388–97. https://doi.org/10.3762/bjnano.5.248.

    Article  Google Scholar 

  76. Aggarwal P, Hall JB, McLeland CB, Dobrovolskaia MA, McNeil SE. Nanoparticle interaction with plasma proteins as it relates to particle biodistribution, biocompatibility and therapeutic efficacy. Adv Drug Deliver Rev. 2009;61:428–37. https://doi.org/10.1016/j.addr.2009.03.009.

    Article  Google Scholar 

  77. Pan Y, Neuss S, Leifert A, Fischler M, Wen F, Simon U, Schmid G, Brandau W, Jahnen-Dechent W. Size-dependent cytotoxicity of gold nanoparticles. Small. 2007;3:1941–9. https://doi.org/10.1002/smll.200700378.

    Article  Google Scholar 

  78. Park J, Lim DH, Lim HJ, Kwon T, Choi JS, Jeong S, Choi IH, Cheon J. Size dependent macrophage responses and toxicological effects of Ag nanoparticles. Chem Commun (Camb). 2011;47:4382–4. https://doi.org/10.1039/c1cc10357a.

    Article  Google Scholar 

  79. Win KY, Feng SS. Effects of particle size and surface coating on cellular uptake of polymeric nanoparticles for oral delivery of anticancer drugs. Biomaterials. 2005;26:2713–22. https://doi.org/10.1016/j.biomaterials.2004.07.050.

    Article  Google Scholar 

  80. Foged C, Brodin B, Frokjaer S, Sundblad A. Particle size and surface charge affect particle uptake by human dendritic cells in an in vitro model. Int J Pharm. 2005;298:315–22. https://doi.org/10.1016/j.ijpharm.2005.03.035.

    Article  Google Scholar 

  81. Petri-Fink A, Chastellain M, Juillerat-Jeanneret L, Ferrari A, Hofmann H. Development of functionalized superparamagnetic iron oxide nanoparticles for interaction with human cancer cells. Biomaterials. 2005;26:2685–94. https://doi.org/10.1016/j.biomaterials.2004.07.023.

    Article  Google Scholar 

  82. Varkouhi AK, Scholte M, Storm G, Haisma HJ. Endosomal escape pathways for delivery of biologicals. J Control Release. 2011;151:220–8. https://doi.org/10.1016/j.jconrel.2010.11.004.

    Article  Google Scholar 

  83. Sharma A, Madhunapantula SV, Robertson GP. Toxicological considerations when creating nanoparticle-based drugs and drug delivery systems. Expert Opin Drug Met. 2012;8:47–69. https://doi.org/10.1517/17425255.2012.637916.

    Article  Google Scholar 

  84. Lunov O, Syrovets T, Loos C, Nienhaus GU, Mailander V, Landfester K, Rouis M, Simmet T. Amino-functionalized polystyrene nanoparticles activate the NLRP3 inflammasome in human macrophages. ACS Nano. 2011;5:9648–57. https://doi.org/10.1021/nn203596e.

    Article  Google Scholar 

  85. Lv H, Zhang S, Wang B, Cui S, Yan J. Toxicity of cationic lipids and cationic polymers in gene delivery. J Control Release. 2006;114:100–9. https://doi.org/10.1016/j.jconrel.2006.04.014.

    Article  Google Scholar 

  86. Tousignant JD, Gates AL, Ingram LA, Johnson CL, Nietupski JB, Cheng SH, Eastman SJ, Scheule RK. Comprehensive analysis of the acute toxicities induced by systemic administration of cationic lipid: plasmid DNA complexes in mice. Hum Gene Ther. 2000;11:2493–513. https://doi.org/10.1089/10430340050207984.

    Article  Google Scholar 

  87. Wei XW, Shao B, He ZY, Ye TH, Luo M, Sang YX, Liang X, Wang W, Luo ST, Yang SY, et al. Cationic nanocarriers induce cell necrosis through impairment of Na+/K+-ATPase and cause subsequent inflammatory response. Cell Res. 2015;25:237–53. https://doi.org/10.1038/cr.2015.9.

    Article  Google Scholar 

  88. Luo D, Saltzman WM. Synthetic DNA delivery systems. Nat Biotechnol. 2000;18:33–7. https://doi.org/10.1038/71889.

    Article  Google Scholar 

  89. Yeung T, Gilbert GE, Shi J, Silvius J, Kapus A, Grinstein S. Membrane phosphatidylserine regulates surface charge and protein localization. Science. 2008;319:210–3. https://doi.org/10.1126/science.1152066.

    Article  Google Scholar 

  90. Musyanovych A, Dausend J, Dass M, Walther P, Mailander V, Landfester K. Criteria impacting the cellular uptake of nanoparticles: a study emphasizing polymer type and surfactant effects. Acta Biomater. 2011;7:4160–8. https://doi.org/10.1016/j.actbio.2011.07.033.

    Article  Google Scholar 

  91. Ehrenberg MS, Friedman AE, Finkelstein JN, Oberdorster G, McGrath JL. The influence of protein adsorption on nanoparticle association with cultured endothelial cells. Biomaterials. 2009;30:603–10. https://doi.org/10.1016/j.biomaterials.2008.09.050.

    Article  Google Scholar 

  92. Chen ZP, Xu RZ, Zhang Y, Gu N. Effects of proteins from culture medium on surface property of silanes-functionalized magnetic nanoparticles. Nanoscale Res Lett. 2009;4:204–9. https://doi.org/10.1007/s11671-008-9226-1.

    Article  Google Scholar 

  93. Kustermann E, Himmelreich U, Kandal K, Geelen T, Ketkar A, Wiedermann D, Strecker C, Esser J, Arnhold S, Hoehn M. Efficient stem cell labeling for MRI studies. Contrast Media Mol Imaging. 2008;3:27–37. https://doi.org/10.1002/cmmi.229.

    Article  Google Scholar 

  94. Babic M, Horak D, Trchova M, Jendelova P, Glogarova K, Lesny P, Herynek V, Hajek M, Sykova E. Poly(l-lysine)-modified iron oxide nanoparticles for stem cell labeling. Bioconjug Chem. 2008;19:740–50. https://doi.org/10.1021/bc700410z.

    Article  Google Scholar 

  95. Arbab AS, Yocum GT, Rad AM, Khakoo AY, Fellowes V, Read EJ, Frank JA. Labeling of cells with ferumoxides–protamine sulfate complexes does not inhibit function or differentiation capacity of hematopoietic or mesenchymal stem cells. NMR Biomed Int J Devoted Dev Appl Magn Reson In vivo. 2005;18:553–9.

    Google Scholar 

  96. Liu G, Gilad AA, Bulte JW, van Zijl PC, McMahon MT. High-throughput screening of chemical exchange saturation transfer MR contrast agents. Contrast Media Mol Imaging. 2010;5:162–70.

    Article  Google Scholar 

  97. Kraitchman DL, Heldman AW, Atalar E, Amado LC, Martin BJ, Pittenger MF, Hare JM, Bulte JW. In vivo magnetic resonance imaging of mesenchymal stem cells in myocardial infarction. Circulation. 2003;107:2290–3. https://doi.org/10.1161/01.CIR.0000070931.62772.4E.

    Article  Google Scholar 

  98. Arbab AS, Bashaw LA, Miller BR, Jordan EK, Bulte JW, Frank JA. Intracytoplasmic tagging of cells with ferumoxides and transfection agent for cellular magnetic resonance imaging after cell transplantation: methods and techniques. Transplantation. 2003;76:1123–30. https://doi.org/10.1097/01.TP.0000089237.39220.83.

    Article  Google Scholar 

  99. Arbab AS, Yocum GT, Wilson LB, Parwana A, Jordan EK, Kalish H, Frank JA. Comparison of transfection agents in forming complexes with ferumoxides, cell labeling efficiency, and cellular viability. Mol Imaging. 2004;3:24–32. https://doi.org/10.1162/153535004773861697.

    Article  Google Scholar 

  100. Zauner W, Ogris M, Wagner E. Polylysine-based transfection systems utilizing receptor-mediated delivery. Adv Drug Deliver Rev. 1998;30:97–113. https://doi.org/10.1016/S0169-409x(97)00110-5.

    Article  Google Scholar 

  101. Jiang XE, Musyanovych A, Rocker C, Landfester K, Mailander V, Nienhaus GU. Specific effects of surface carboxyl groups on anionic polystyrene particles in their interactions with mesenchymal stem cells. Nanoscale. 2011;3:2028–35. https://doi.org/10.1039/c0nr00944j.

    Article  Google Scholar 

  102. Jiang XE, Dausend J, Hafner M, Musyanovych A, Rocker C, Landfester K, Mailander V, Nienhaus GU. Specific effects of surface amines on polystyrene nanoparticles in their interactions with mesenchymal stem cells. Biomacromol. 2010;11:748–53. https://doi.org/10.1021/bm901348z.

    Article  Google Scholar 

  103. Zhang R, Wang S, Yang Y, Deng Y, Li D, Su P, Yang Y. Modification of polydopamine-coated Fe3O4 nanoparticles with multi-walled carbon nanotubes for magnetic-μ-dispersive solid-phase extraction of antiepileptic drugs in biological matrices. Anal Bioanal Chem. 2018;410:3779–88.

    Article  Google Scholar 

  104. Chen Y, Zhang F, Wang Q, Lin H, Tong R, An N, Qu F. The synthesis of LA-Fe3O4@ PDA-PEG-DOX for photothermal therapy–chemotherapy. Dalton Trans. 2018;47:2435–43.

    Article  Google Scholar 

  105. Jones M, Leroux J. Polymeric micelles—a new generation of colloidal drug carriers. Eur J Pharm Biopharm. 1999;48:101–11. https://doi.org/10.1016/s0939-6411(99)00039-9.

    Article  Google Scholar 

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Acknowledgements

This work was supported by Grants from the National Research Foundation of Korea (NRF), No. 2018R1D1A1B07042339 and 2019K2A9A2A08000123.

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  1. Department of Biomedical Engineering, Yonsei University, 1 Yonseidae-gil, Wonju, Gangwon-do, South Korea

    Wan Su Yun, Susmita Aryal & Jaehong Key

  2. Research Institute of Hearing Enhancement, Yonsei University Wonju College of Medicine, Wonju, South Korea

    Ye Ji Ahn & Young Joon Seo

  3. Department of Otorhinolaryngology, Yonsei University Wonju College of Medicine, Wonju, South Korea

    Ye Ji Ahn & Young Joon Seo

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  1. Wan Su Yun
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Yun, W.S., Aryal, S., Ahn, Y. et al. Engineered iron oxide nanoparticles to improve regenerative effects of mesenchymal stem cells. Biomed. Eng. Lett. 10, 259–273 (2020). https://doi.org/10.1007/s13534-020-00153-w

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