Nanoengineered Sprayable Therapy for Treating Myocardial Infarction

Marcelo Muñoz; Cagla Eren Cimenci; Keshav Goel; Maxime Comtois-Bona; Mahir Hossain; Christopher McTiernan; Matias Zuñiga-Bustos; Alex Ross; Brenda Truong; Darryl R. Davis; Wenbin Liang; Benjamin Rotstein; Marc Ruel; Horacio Poblete; Erik J. Suuronen; Emilio I. Alarcon

doi:10.1021/acsnano.1c08890

journal article·2022-03-22Open access

Nanoengineered Sprayable Therapy for Treating Myocardial Infarction

Marcelo Muñoz, Cagla Eren Cimenci, Keshav Goel, Maxime Comtois-Bona, Mahir Hossain, Christopher McTiernan, Matias Zuñiga-Bustos, Alex Ross, Brenda Truong, Darryl R. Davis, Wenbin Liang, Benjamin Rotstein, Marc Ruel, Horacio Poblete, Erik J. Suuronen, Emilio I. Alarcon

ACS Nano· Volume 16· Issue 3

Publisher page Open full text

Source abstract

Abstract

We report the development, as well as the in vitro and in vivo testing, of a sprayable nanotherapeutic that uses surface engineered custom-designed multiarmed peptide grafted nanogold for on-the-spot coating of an infarcted myocardial surface. When applied to mouse hearts, 1 week after infarction, the spray-on treatment resulted in an increase in cardiac function (2.4-fold), muscle contractility, and myocardial electrical conductivity. The applied nanogold remained at the treatment site 28 days postapplication with no off-target organ infiltration. Further, the infarct size in the mice that received treatment was found to be <10% of the total left ventricle area, while the number of blood vessels, prohealing macrophages, and cardiomyocytes increased to levels comparable to that of a healthy animal. Our cumulative data suggest that the therapeutic action of our spray-on nanotherapeutic is highly effective, and in practice, its application is simpler than other regenerative approaches for treating an infarcted heart.

Source: europepmc · Quality: candidate unverified · Source record ↗

Research context

Nanomaterials

OpenAlex topics: Tissue Engineering and Regenerative Medicine · Electrospun Nanofibers in Biomedical Applications · Graphene and Nanomaterials Applications

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

Affiliations

BEaTS Research, Division of Cardiac Surgery, University of Ottawa Heart Institute, Ottawa, Ontario K1Y 4W7, Canada

Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada

Departamento de Bioinformática, Centro de Bioinformática, Simulación y Modelado (CBSM), Facultad de Ingeniería, Universidad de Talca, Campus Talca, 2 Norte 685, 3460000, Talca, Chile

University of Ottawa Heart Institute, Division of Cardiology, Department of Medicine, University of Ottawa, Ottawa, Ontario K1Y 4W7, Canada

Cardiac Electrophysiology Lab, University of Ottawa, Ottawa, Ontario K1Y 4W7, Canada

Department of Biochemistry, Microbiology, and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada

Molecular Imaging Probes and Radiochemistry Laboratory, University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, Ontario K1Y 4W7, Canada

Millennium Nucleus of Ion Channels-Associated Diseases (MiNICAD), Universidad de Talca, 2 Norte 685, 3460000 Talca, Chile

Funding

Canadian Institutes of Health Research · Social Sciences and Humanities Research Council of Canada · Natural Sciences and Engineering Research Council of Canada · Fondo Nacional de Desarrollo Cient?fico y Tecnol?gico · Government of Ontario

References (100+)

Show source-provided references

1. World Health Organization. Noncommunicable Diseases. http://www.who.int/mediacentre/factsheets/fs355/en/ (accessed November 2021).

2. World Health Organization. The top 10 causes of death. https://www.who.int/news-room/fact-sheets/detail/the-top-10-causes-of-death (accessed November 2021).

3. Public Health Agency of Canada. Six Types of Cardiovascular Disease. http://www.phac-aspc.gc.ca/cd-mc/cvd-mcv/cvd-mcv-eng.php (accessed November 2021).

4. 10.1016/j.semcdb.2019.09.00310.1016/j.semcdb.2019.09.003 ↗

5. 10.1161/CIR.000000000000015210.1161/CIR.0000000000000152 ↗

6. Heart & Stroke Foundation. The burden of Heart Failure. https://www.heartandstroke.ca/-/media/pdf-files/canada/2017-heart-month/heartandstroke-reportonhealth-2016.ashx?la=en&hash=91708486C1BC014E24AB4E719B47AEEB8C5EB93E (accessed November 2021).

7. 10.1001/jamacardio.2020.355710.1001/jamacardio.2020.3557 ↗

8. 10.1016/j.ijcha.2020.10057810.1016/j.ijcha.2020.100578 ↗

9. 10.1001/jamacardio.2020.362910.1001/jamacardio.2020.3629 ↗

10. 10.1021/acsami.8b1884410.1021/acsami.8b18844 ↗

11. 10.1038/nnano.2011.16010.1038/nnano.2011.160 ↗

12. 10.1021/nl502673m10.1021/nl502673m ↗

13. 10.1021/nn103531210.1021/nn1035312 ↗

14. 10.1016/j.msec.2016.02.05610.1016/j.msec.2016.02.056 ↗

15. 10.1113/eph870238510.1113/eph8702385 ↗

16. 10.1369/002215541349391210.1369/0022155413493912 ↗

17. 10.1161/CIRCRESAHA.116.30357710.1161/CIRCRESAHA.116.303577 ↗

18. 10.1016/j.yjmcc.2009.07.01510.1016/j.yjmcc.2009.07.015 ↗

19. 10.1021/acsbiomaterials.9b0128110.1021/acsbiomaterials.9b01281 ↗

20. 10.1039/D0RA03659E10.1039/D0RA03659E ↗

21. 10.1016/j.biotechadv.2019.02.01110.1016/j.biotechadv.2019.02.011 ↗

22. 10.1021/acsami.9b0394210.1021/acsami.9b03942 ↗

23. 10.1039/C7RA08960K10.1039/C7RA08960K ↗

24. 10.1039/C7TB00405B10.1039/C7TB00405B ↗

25. 10.1039/C7TB02349A10.1039/C7TB02349A ↗

26. 10.1021/acs.langmuir.5b0360110.1021/acs.langmuir.5b03601 ↗

27. 10.1039/C6NR01339B10.1039/C6NR01339B ↗

28. 10.1007/s10439-016-1583-910.1007/s10439-016-1583-9 ↗

29. 10.1039/c3gc41360h10.1039/c3gc41360h ↗

30. 10.1021/acsnano.7b0862010.1021/acsnano.7b08620 ↗

31. 10.1016/j.theriogenology.2020.12.02710.1016/j.theriogenology.2020.12.027 ↗

32. 10.1021/mp200104410.1021/mp2001044 ↗

33. 10.1167/iovs.05-015510.1167/iovs.05-0155 ↗

34. Swanson K. I. · Invest. Ophthalmol. Vis. Sci. · 2004 · 45 · 84910.1167/iovs.03-0374 ↗

35. Tris (2-carboxyethyl) phosphine-HCl; Safety Data Sheet; G-Biosciences: St. Louis, MO, 2012.https://www.gbiosciences.com/image/pdfs/msds/786-874_msds.pdf (accessed November 2021).

36. Marini, J. L.; Saxena, S. J. Luminate Eye Gel. US 10034825 B2, 2015.

37. 10.3109/15569527.2011.62938410.3109/15569527.2011.629384 ↗

38. 10.1016/j.actbio.2013.04.01410.1016/j.actbio.2013.04.014 ↗

39. 10.1038/s41598-019-47059-x10.1038/s41598-019-47059-x ↗

40. 10.1016/j.jhsa.2015.06.11710.1016/j.jhsa.2015.06.117 ↗

41. 10.1016/j.ejpb.2019.01.02410.1016/j.ejpb.2019.01.024 ↗

42. Fischer M. J. E. · 2010 · 5510.1007/978-1-60761-670-2_3 ↗

43. 10.1038/s41467-019-12748-810.1038/s41467-019-12748-8 ↗

44. 10.1021/ja066522h10.1021/ja066522h ↗

45. 10.1038/s41598-019-48748-310.1038/s41598-019-48748-3 ↗

46. 10.1038/s41598-017-03015-110.1038/s41598-017-03015-1 ↗

47. 10.1016/j.bbrep.2021.10099110.1016/j.bbrep.2021.100991 ↗

48. 10.1007/s12274-014-0697-310.1007/s12274-014-0697-3 ↗

49. 10.1021/nn404055310.1021/nn4040553 ↗

50. 10.1186/s12916-019-1268-y10.1186/s12916-019-1268-y ↗

51. 10.1161/01.ATV.0000223901.08459.5710.1161/01.ATV.0000223901.08459.57 ↗

52. 10.1016/j.biomaterials.2012.05.03210.1016/j.biomaterials.2012.05.032 ↗

53. 10.1016/j.copbio.2013.03.01110.1016/j.copbio.2013.03.011 ↗

54. Wang J. J. · 2014 · 1710.1533/9780857096715.1.17 ↗

55. 10.1161/CIRCULATIONAHA.110.93951210.1161/CIRCULATIONAHA.110.939512 ↗

56. 10.1016/j.jacc.2009.06.01010.1016/j.jacc.2009.06.010 ↗

57. 10.1016/j.biomaterials.2015.08.01110.1016/j.biomaterials.2015.08.011 ↗

58. 10.1002/mabi.20130022310.1002/mabi.201300223 ↗

59. 10.1016/j.ahj.2015.08.01710.1016/j.ahj.2015.08.017 ↗

60. 10.1093/eurheartj/ehv25910.1093/eurheartj/ehv259 ↗

61. 10.1371/journal.pone.002157110.1371/journal.pone.0021571 ↗

62. 10.1002/term.38310.1002/term.383 ↗

63. 10.1016/j.msec.2014.06.00410.1016/j.msec.2014.06.004 ↗

64. 10.1016/j.msec.2014.07.06110.1016/j.msec.2014.07.061 ↗

65. 10.1163/15685620677487918010.1163/156856206774879180 ↗

66. 10.1021/nn305559j10.1021/nn305559j ↗

67. 10.1016/j.actbio.2017.06.03610.1016/j.actbio.2017.06.036 ↗

68. 10.1161/CIRCULATIONAHA.114.01493710.1161/CIRCULATIONAHA.114.014937 ↗

69. 10.1021/nl204064s10.1021/nl204064s ↗

70. 10.1016/j.actbio.2011.04.02810.1016/j.actbio.2011.04.028 ↗

71. 10.1021/nl201514a10.1021/nl201514a ↗

72. 10.2147/IJN.S3457410.2147/IJN.S34574 ↗

73. 10.1002/adma.20150325510.1002/adma.201503255 ↗

74. 10.1002/adfm.20150036510.1002/adfm.201500365 ↗

75. 10.1039/C5NR07059G10.1039/C5NR07059G ↗

76. 10.3109/17435390.2016.117267810.3109/17435390.2016.1172678 ↗

77. 10.1073/pnas.161640011310.1073/pnas.1616400113 ↗

78. 10.1177/109158181986313010.1177/1091581819863130 ↗

79. 10.1016/j.biomaterials.2012.03.03310.1016/j.biomaterials.2012.03.033 ↗

80. 10.1039/C4NR01284D10.1039/C4NR01284D ↗

81. 10.1039/C7CC08629F10.1039/C7CC08629F ↗

82. 10.3390/nano1009167110.3390/nano10091671 ↗

83. 10.3390/ijms1907197910.3390/ijms19071979 ↗

84. 10.1038/srep2020310.1038/srep20203 ↗

85. Turner P. V. · J. Am. Assoc. Lab. Animal Sci. · 2011 · 50 · 614

86. Hirota J. · 2012 · 70910.1016/B978-0-12-382008-2.00030-1 ↗

87. 10.3791/277110.3791/2771 ↗

88. Turner P. V. · J. Am. Assoc. Lab. Animal Sci. · 2011 · 50 · 600

89. 10.1089/ten.tec.2016.049210.1089/ten.tec.2016.0492 ↗

90. 10.1016/j.hrthm.2017.11.03110.1016/j.hrthm.2017.11.031 ↗

91. 10.3389/fphys.2016.0038910.3389/fphys.2016.00389 ↗

92. 10.1109/TBME.2004.82803010.1109/TBME.2004.828030 ↗

93. 10.1152/ajpheart.2001.280.1.H17910.1152/ajpheart.2001.280.1.H179 ↗

94. 10.1161/01.CIR.96.9.307910.1161/01.CIR.96.9.3079 ↗

95. 10.1152/ajpheart.00754.201510.1152/ajpheart.00754.2015 ↗

96. 10.1161/CIRCEP.117.00466510.1161/CIRCEP.117.004665 ↗

97. 10.14814/phy2.1386010.14814/phy2.13860 ↗

98. 10.1016/j.cardiores.2003.11.03510.1016/j.cardiores.2003.11.035 ↗

99. 10.1016/S1567-5394(02)00152-410.1016/S1567-5394(02)00152-4 ↗

100. 10.1016/j.jacc.2020.04.01110.1016/j.jacc.2020.04.011 ↗