journal article·2020-12Open access

Intracerebral Injection of Graphene Oxide Nanosheets Mitigates Microglial Activation Without Inducing Acute Neurotoxicity: A Pilot Comparison to Other Nanomaterials

Corinne Portioli, Cyrill Bussy, Mariarosa Mazza, Neus Lozano, Dhifaf A. Jasim, Maurizio Prato, Alberto Bianco, Marina Bentivoglio, Kostas Kostarelos

Small· Volume 16· Issue 48

Abstract

Abstract Carbon‐based nanomaterials (CNMs) are being explored for neurological applications. However, systematic in vivo studies investigating the effects of CNM nanocarriers in the brain and how brain cells respond to such nanomaterials are scarce. To address this, functionalized multiwalled carbon nanotubes and graphene oxide (GO) sheets are injected in mice brain and compared with charged liposomes. The induction of acute neuroinflammatory and neurotoxic effects locally and in brain structures distant from the injection site are assessed up to 1 week postadministration. While significant neuronal cell loss and sustained microglial cell activation are observed after injection of cationic liposomes, none of the tested CNMs induces either neurodegeneration or microglial activation. Among the candidate nanocarriers tested, GO sheets appear to elicit the least deleterious neuroinflammatory profile. At molecular level, GO induces moderate activation of proinflammatory markers compared to vehicle control. At histological level, brain response to GO is lower than after vehicle control injection, suggesting some capacity for GO to reduce the impact of stereotactic injection on brain. While these findings are encouraging and valuable in the selection and design of nanomaterial‐based brain delivery systems, they warrant further investigations to better understand the mechanisms underlying GO immunomodulatory properties in brain.
Source: crossref · Quality: baseline

Research context

OpenAlex topics: Graphene and Nanomaterials Applications · Nanoparticles: synthesis and applications · Advanced Nanomaterials in Catalysis

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Nanomedicine Lab School of Health Sciences Faculty of Biology, Medicine and Health The University of Manchester Manchester M13 9PL UK

Department of Neurosciences Biomedicine and Movement Sciences University of Verona Verona 37134 Italy

National Graphene Institute The University of Manchester Manchester M13 9PL UK

Lydia Becker Institute of Immunology and Inflammation Faculty of Biology, Medicine and Health The University of Manchester Manchester M13 9PL UK

Catalan Institute of Nanoscience and Nanotechnology (ICN2) and The Barcelona Institute of Science and Technology (BIST) Campus UAB Bellaterra Barcelona 08193 Spain

Department of Chemical and Pharmaceutical Sciences University of Trieste Trieste 34127 Italy

Center for Cooperative Research in Biomaterials (CIC biomaGUNE) Basque Research and Technology Alliance (BRTA) Paseo de Miramón 182 Donostia‐San Sebastián 20014 Spain

Ikerbasque, Basque Foundation for Science Bilbao 48009 Spain

CNRS Immunology, Immunopathology and Therapeutic Chemistry UPR3572, ISIS University of Strasbourg Strasbourg 67000 France

Funding

Horizon 2020 Framework Programme · Centre National de la Recherche Scientifique · Centre International de Recherche aux Frontières de la Chimie · Agence Nationale de la Recherche · AXA Research Fund · Ministerio de Economía y Competitividad · Università degli Studi di Trieste · Agencia Estatal de Investigación · Fondazione Cassa di Risparmio di Verona Vicenza Belluno e Ancona · Università degli Studi di Verona

References (84)

Show source-provided references
1. 10.1002/adma.20180136210.1002/adma.201801362 ↗
2. 10.1016/j.addr.2013.09.00610.1016/j.addr.2013.09.006 ↗
3. 10.1016/j.addr.2011.11.01410.1016/j.addr.2011.11.014 ↗
4. 10.1166/jnn.2014.911910.1166/jnn.2014.9119 ↗
5. 10.1016/j.pneurobio.2009.05.00210.1016/j.pneurobio.2009.05.002 ↗
6. 10.2217/nnm.14.19510.2217/nnm.14.195 ↗
7. 10.2217/nnm.15.11410.2217/nnm.15.114 ↗
8. 10.1016/bs.irn.2016.07.00110.1016/bs.irn.2016.07.001 ↗
9. 10.1016/j.addr.2013.08.00510.1016/j.addr.2013.08.005 ↗
10. 10.3389/fnsys.2018.0001210.3389/fnsys.2018.00012 ↗
11. 10.1039/b410943k10.1039/b410943k ↗
12. 10.1016/j.cbpa.2005.10.00510.1016/j.cbpa.2005.10.005 ↗
13. 10.1016/j.addr.2006.09.01510.1016/j.addr.2006.09.015 ↗
14. 10.1038/nnano.2014.22410.1038/nnano.2014.224 ↗
15. 10.1586/14737175.2014.92580410.1586/14737175.2014.925804 ↗
16. 10.1016/j.jfda.2014.01.00910.1016/j.jfda.2014.01.009 ↗
17. 10.1021/am300756510.1021/am3007565 ↗
18. 10.1016/j.nano.2014.08.00110.1016/j.nano.2014.08.001 ↗
19. 10.1016/j.biomaterials.2012.01.02510.1016/j.biomaterials.2012.01.025 ↗
20. 10.1007/s00726-015-1970-910.1007/s00726-015-1970-9 ↗
21. 10.1021/nl501839q10.1021/nl501839q ↗
22. 10.1073/pnas.110093010810.1073/pnas.1100930108 ↗
23. 10.1016/j.nano.2009.11.00710.1016/j.nano.2009.11.007 ↗
24. 10.1016/j.biomaterials.2015.02.08310.1016/j.biomaterials.2015.02.083 ↗
25. 10.2147/IJN.S6842910.2147/IJN.S68429 ↗
26. 10.1016/j.jconrel.2016.01.03110.1016/j.jconrel.2016.01.031 ↗
27. 10.1016/j.jconrel.2015.12.03910.1016/j.jconrel.2015.12.039 ↗
28. 10.1039/C5NR06282A10.1039/C5NR06282A ↗
29. 10.1002/adma.20110486410.1002/adma.201104864 ↗
30. 10.1002/adma.20120322910.1002/adma.201203229 ↗
31. 10.1021/am402128s10.1021/am402128s ↗
32. 10.1021/acsnano.9b0807810.1021/acsnano.9b08078 ↗
33. 10.1016/j.biotechadv.2015.02.00410.1016/j.biotechadv.2015.02.004 ↗
34. 10.1038/nm.439710.1038/nm.4397 ↗
35. 10.1016/j.brainresrev.2010.09.00810.1016/j.brainresrev.2010.09.008 ↗
36. 10.1016/j.nano.2008.06.00810.1016/j.nano.2008.06.008 ↗
37. 10.1371/journal.pone.008096410.1371/journal.pone.0080964 ↗
38. 10.1155/2015/10413510.1155/2015/104135 ↗
39. 10.1371/journal.pone.012915610.1371/journal.pone.0129156 ↗
40. 10.1021/acsnano.5b0235810.1021/acsnano.5b02358 ↗
41. 10.1016/j.colsurfb.2015.03.02210.1016/j.colsurfb.2015.03.022 ↗
42. 10.1021/acsnano.6b0013010.1021/acsnano.6b00130 ↗
43. 10.1021/acsnano.6b0343810.1021/acsnano.6b03438 ↗
44. 10.1021/acs.nanolett.8b0248710.1021/acs.nanolett.8b02487 ↗
45. 10.1021/acsnano.8b0364210.1021/acsnano.8b03642 ↗
46. 10.1016/j.jconrel.2006.04.01410.1016/j.jconrel.2006.04.014 ↗
47. 10.1016/S0005-2736(97)00126-010.1016/S0005-2736(97)00126-0 ↗
48. Knudsen K. B. · Nanotoxicology · 2014 · 8 · 764
49. 10.1016/j.nano.2014.08.00410.1016/j.nano.2014.08.004 ↗
50. 10.1021/acs.nanolett.8b0490310.1021/acs.nanolett.8b04903 ↗
51. 10.1016/j.bbamem.2005.10.00810.1016/j.bbamem.2005.10.008 ↗
52. 10.1039/c1cc13011k10.1039/c1cc13011k ↗
53. 10.2217/nnm.12.3310.2217/nnm.12.33 ↗
54. 10.1007/s00204-012-0860-010.1007/s00204-012-0860-0 ↗
55. 10.1039/C5NR06625E10.1039/C5NR06625E ↗
56. 10.1088/2053-1583/3/1/01400610.1088/2053-1583/3/1/014006 ↗
57. 10.1088/2053-1583/aac05c10.1088/2053-1583/aac05c ↗
58. 10.1023/B:NEON.0000024743.56415.4b10.1023/B:NEON.0000024743.56415.4b ↗
59. 10.1016/j.biomaterials.2014.11.05110.1016/j.biomaterials.2014.11.051 ↗
60. 10.1016/S0006-8993(00)02513-010.1016/S0006-8993(00)02513-0 ↗
61. 10.1016/j.ymthe.2017.03.01110.1016/j.ymthe.2017.03.011 ↗
62. 10.1002/admi.20190022910.1002/admi.201900229 ↗
63. 10.2217/nnm.14.9110.2217/nnm.14.91 ↗
64. 10.2217/17435889.1.3.29710.2217/17435889.1.3.297 ↗
65. 10.1016/j.neuroscience.2004.09.05310.1016/j.neuroscience.2004.09.053 ↗
66. 10.1007/s00401-009-0619-810.1007/s00401-009-0619-8 ↗
67. 10.1038/nrn203810.1038/nrn2038 ↗
68. 10.1016/j.biomaterials.2009.08.05010.1016/j.biomaterials.2009.08.050 ↗
69. 10.1106/RA7U-1V9C-RV7C-8QXL10.1106/RA7U-1V9C-RV7C-8QXL ↗
70. 10.1021/acsnano.8b0475810.1021/acsnano.8b04758 ↗
71. 10.1021/ar300199e10.1021/ar300199e ↗
72. 10.1007/s11356-020-08036-410.1007/s11356-020-08036-4 ↗
73. 10.1039/b209843a10.1039/b209843a ↗
74. 10.1016/j.carbon.2008.03.01010.1016/j.carbon.2008.03.010 ↗
75. 10.1021/ja304499q10.1021/ja304499q ↗
76. 10.1016/0003-2697(70)90146-610.1016/0003-2697(70)90146-6 ↗
77. Paxinos G. · 2012
78. 10.1006/meth.2001.126210.1006/meth.2001.1262 ↗
79. 10.1523/JNEUROSCI.23-27-09162.200310.1523/JNEUROSCI.23-27-09162.2003 ↗
80. 10.1002/glia.2035810.1002/glia.20358 ↗
81. 10.1016/S0006-8993(03)03198-610.1016/S0006-8993(03)03198-6 ↗
82. 10.1016/j.brainresprot.2005.10.00210.1016/j.brainresprot.2005.10.002 ↗
83. 10.1016/j.brainres.2006.06.01410.1016/j.brainres.2006.06.014 ↗
84. 10.1007/s00429-012-0500-810.1007/s00429-012-0500-8 ↗