REVIEW ARTICLE Monocyte-mediated drug delivery systems for the treatment of cardiovascular diseases Gil Aizik 1 & Etty Grad 1 & Gershon Golomb 1 # Controlled Release Society 2017 Abstract Major advances have been achieved in understand- ing the mechanisms and risk factors leading to cardiovas- cular disorders and consequently developing new therapies. A strong inflammatory response occurs with a substantial recruit- ment 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 phagocy- tosis, and the release of inflammatory cytokines and reac- tive oxygen species. In this review, we will focus on deliv- ery 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 nanopar- ticles and liposomes for the therapy of myocardial infarc- tion 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. Keywords Drug delivery systems . Liposomes . Polymeric nanoparticles . Monocytes . Monocyte subpopulations . Vascular injury 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 N c 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 Cardiovascular disorders Cardiovascular diseases (CVDs) are a global pandemic with more than 92 million Americans living with some * Gershon Golomb gershong@ekmd.huji.ac.il 1 Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, 9112001 Jerusalem, Israel Drug Deliv. and Transl. Res. https://doi.org/10.1007/s13346-017-0431-2