Nanoimmunotherapy to treat ischaemic heart disease

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Abstract

Atherosclerosis is a chronic disease of the large arteries and the underlying cause of myocardial infarction and stroke. Atherosclerosis is driven by cholesterol accumulation and subsequent inflammation in the vessel wall. Despite the clinical successes of lipid-lowering treatments, atherosclerosis remains one of the major threats to human health worldwide. Over the past 20 years, insights into cardiovascular immunopathology have provided a plethora of new potential therapeutic targets to reduce the risk of atherosclerosis and have shifted the therapeutic focus from lipids to inflammation. In 2017, the CANTOS trial demonstrated for the first time the beneficial effects of targeting inflammation to treat cardiovascular disease by showing that IL-1β inhibition can reduce the recurrence rate of cardiovascular events in a large cohort of patients. At the same time, preclinical studies have highlighted nanotechnology approaches that facilitate the specific targeting of innate immune cells, which could potentially generate more effective immunomodulatory treatments to induce disease regression and prevent the recurrence of cardiovascular events. The clinical translation of such nanoimmunotherapies and their application to treat patients with ischaemic heart disease are challenges that lie ahead.

Key points

  • The therapeutic focus in atherosclerosis has shifted from lipid lowering to treating inflammation.

  • In the past decade, novel therapeutic targets for atherosclerosis have been identified as our understanding of the complex immune processes involved in this pathology has increased.

  • Advances in bioengineering have yielded innovative techniques to produce libraries of nanomaterials that engage immune cells.

  • The combined advances in nanoengineering and immunobiology have fuelled the development of novel nanoimmunotherapies, mainly aimed at modulating innate immune responses in cardiovascular diseases.

  • Large studies in animal models focusing on efficacy as well as safety are required to pave the way for clinical translation of cardiovascular nanoimmunotherapy.

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Fig. 1: Cardiovascular immunopathology.
Fig. 2: HDL nanobiologic library.
Fig. 3: Nanotherapeutic approaches to reduce atherosclerotic plaque inflammation.
Fig. 4: Highlighted studies using nanotechnology to resolve inflammation in cardiovascular disease.
Fig. 5: Potential clinical applications of nanoimmunomodulating therapies.

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Acknowledgements

The authors are supported by grants from the Netherlands Organization for Scientific Research: ZonMW Veni 016156059 (R.D.), ZonMW Vidi 91713324 (W.J.M.M.), and ZonMW Vici 91818622 (W.J.M.M.); AHA grant 17PRE33660729 and the Foundation “De Drie Lichten” in the Netherlands (M.L.S.); AHA grant 16SDG31390007 (C.P.M.); NIH grants R01 HL118440, R01 HL125703, and P01 HL131478 (W.J.M.M.), R01 EB009638 (Z.A.F.), and R01 HL144072 (W.J.M.M. and Z.A.F.); NIH Program of Excellence in Nanotechnology (PEN) Award HHSN368201000045C (Z.A.F.); and the Massachusetts General Hospital Research Scholar Award (M.N.).

Author information

R.D. and W.J.M.M. wrote the manuscript. M.L.S. designed the figures for initial submission. All the authors reviewed and edited the article before submission.

Correspondence to Raphaël Duivenvoorden or Willem J. M. Mulder.

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7th Framework Programme NanoAthero: http://www.nanoathero.eu.

National Heart, Lung, and Blood Institute’s Program of Excellence in Nanotechnology: http://nhlbi-pen.net.

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Duivenvoorden, R., Senders, M.L., Leent, M.M.T. et al. Nanoimmunotherapy to treat ischaemic heart disease. Nat Rev Cardiol 16, 21–32 (2019) doi:10.1038/s41569-018-0073-1

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