Monocyte-mediated drug delivery systems for the treatment of cardiovascular diseases

Abstract

Major advances have been achieved in understanding the mechanisms and risk factors leading to cardiovascular disorders and consequently developing new therapies. A strong inflammatory response occurs with a substantial recruitment of innate immunity cells in atherosclerosis, myocardial infarction, and restenosis. Monocytes and macrophages are key players in the healing process that ensues following injury. In the inflamed arterial wall, monocytes, and monocyte-derived macrophages have specific functions in the initiation and resolution of inflammation, principally through phagocytosis, and the release of inflammatory cytokines and reactive oxygen species. In this review, we will focus on delivery systems, mainly nanoparticles, for modulating circulating monocytes/monocyte-derived macrophages. We review the different strategies of depletion or modulation of circulating monocytes and monocyte subtypes, using polymeric nanoparticles and liposomes for the therapy of myocardial infarction and restenosis. We will further discuss the strategies of exploiting circulating monocytes for biological targeting of nanocarrier-based drug delivery systems for therapeutic and diagnostic applications.

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Abbreviations

ALN-NPs:

Alendronate nanoparticles

BPs:

Bisphosphonates

CHD:

Coronary heart disease

CM:

Classical monocytes

CVD:

Cardiovascular disease(s)

DDS:

Drug delivery system(s)

DES:

Drug eluting stent

EC:

Endothelial cells

DM:

Diabetes mellitus

EPR:

Enhanced permeability and retention effect

Ga:

Gallium

Gd:

Gadolinium

IM:

Intermediate monocytes

LipALN:

Liposomal alendronate

LipCLOD:

Liposomal clodronate

LipQDs:

Liposomal quantum dots

MI:

Myocardial infraction

MPS:

Mononuclear phagocytic system

Nc :

Number concentration

NCM:

Non-classical monocytes

NPs:

Nanoparticles

PCI:

Percutaneous coronary intervention(s)

PEG:

Polyethylene glycol

PLGA:

Poly(d,l-lactide co-glycolide)

QDs:

Quantum dots

QY:

Quantum yield

siCCR2:

siRNA sequence against CCR2

SMC:

Smooth muscle cells

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Acknowledgements

GG is grateful to the Woll Sisters and Brothers Chair in Cardiovascular Diseases.

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Correspondence to Gershon Golomb.

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EG and GA declare that they have no conflict of interest. GG has a financial stake in Biorest Ltd.

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Aizik, G., Grad, E. & Golomb, G. Monocyte-mediated drug delivery systems for the treatment of cardiovascular diseases. Drug Deliv. and Transl. Res. 8, 868–882 (2018). https://doi.org/10.1007/s13346-017-0431-2

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Keywords

  • Drug delivery systems
  • Liposomes
  • Polymeric nanoparticles
  • Monocytes
  • Monocyte subpopulations
  • Vascular injury