Monocytes and macrophages as nanomedicinal targets for improved diagnosis and treatment of disease

Lameijer, Marnix; Tang, Jun; Nahrendorf, Matthias; Beelen, Robert H.J.; Mulder, Willem J. M.

doi:10.1586/14737159.2013.819216

Cited by 92 publications

(79 citation statements)

References 111 publications

(124 reference statements)

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“…21 Based on the ability of monocytes and macrophages to assimilate foreign particles efficiently, the use of nanoparticles is a promising solution for the management of inflammatory diseases. Compared with free therapeutic agents, drug-loaded Lipo are the most frequently used nanocarrier for targeted drug delivery and provide several advantages, mainly because they improve the pharmacokinetics and bioavailability of these agents.…”

Section: Discussionmentioning

confidence: 99%

Lipopolysaccharide-induced inflammation in monocytes/macrophages is blocked by liposomal delivery of G<sub>i</sub>-protein inhibitor

Pirvulescu¹,

Rebleanu²,

Constantinescu³

et al. 2017

IJN

106

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Background Lipopolysaccharide (LPS) is widely recognized as a potent activator of monocytes/macrophages, and its effects include an altered production of key mediators, such as inflammatory cytokines and chemokines. The involvement of G i protein in mediating LPS effects has been demonstrated in murine macrophages and various cell types of human origin. Purpose The aim of the present work was to evaluate the potential of a G i -protein inhibitor encapsulated in liposomes in reducing the inflammatory effects induced by LPS in monocytes/macrophages. Materials and methods Guanosine 5′- O -(2-thiodiphosphate) (GOT), a guanosine diphosphate analog that completely inhibits G-protein activation by guanosine triphosphate and its analogs, was encapsulated into liposomes and tested for anti-inflammatory effects in LPS-activated THP1 monocytes or THP1-derived macrophages. The viability of monocytes/macrophages after incubation with different concentrations of free GOT or liposome-encapsulated GOT was assessed by MTT assay. MAPK activation and production of IL1β, TNFα, IL6, and MCP1 were assessed in LPS-activated monocytes/macrophages in the presence or absence of free or encapsulated GOT. In addition, the effect of free or liposome-encapsulated GOT on LPS-stimulated monocyte adhesion to activated endothelium and on monocyte chemotaxis was evaluated. Results We report here that GOT-loaded liposomes inhibited activation of MAPK and blocked the production of the cytokines IL1β, TNFα, IL6, and MCP1 induced by LPS in monocytes and macrophages. Moreover, GOT encapsulated in liposomes reduced monocyte adhesion and chemotaxis. All demonstrated events were in contrast with free GOT, which showed reduced or no effect on monocyte/macrophage activation with LPS. Conclusion This study demonstrates the potential of liposomal GOT in blocking LPS proinflammatory effects in monocytes/macrophages.

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Section: Discussionmentioning

confidence: 99%

Lipopolysaccharide-induced inflammation in monocytes/macrophages is blocked by liposomal delivery of G<sub>i</sub>-protein inhibitor

Pirvulescu¹,

Rebleanu²,

Constantinescu³

et al. 2017

IJN

106

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“…Monocytes and macrophages have recently been identified as interesting targets for both diagnosis and treatment of inflammatory diseases such as RA. 77 A directed uptake of specific nanoparticle formulations by monocytes and macrophages, which migrate into the inflamed tissue, is desirable on the one hand for imaging as shown by the NanoDiaRA project results, thereby enabling early diagnosis of RA. 78 On the other hand, conjugation of nanoparticles that invade inflamed tissue with disease modifying drugs may optimize treatment strategies in the future.…”

mentioning

confidence: 99%

Effects of PVA coated nanoparticles on human immune cells

Strehl¹,

Gaber²,

Maurizi³

et al. 2015

IJN

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Nanotechnology provides new opportunities in human medicine, mainly for diagnostic and therapeutic purposes. The autoimmune disease rheumatoid arthritis (RA) is often diagnosed after irreversible joint structural damage has occurred. There is an urgent need for a very early diagnosis of RA, which can be achieved by more sensitive imaging methods. Superparamagnetic iron oxide nanoparticles (SPION) are already used in medicine and therefore represent a promising tool for early diagnosis of RA. The focus of our work was to investigate any potentially negative effects resulting from the interactions of newly developed amino-functionalized amino-polyvinyl alcohol coated (a-PVA) SPION (a-PVA-SPION), that are used for imaging, with human immune cells. We analyzed the influence of a-PVA-SPION with regard to cell survival and cell activation in human whole blood in general, and in human monocytes and macrophages representative of professional phagocytes, using flow cytometry, multiplex suspension array, and transmission electron microscopy. We found no effect of a-PVA-SPION on the viability of human immune cells, but cytokine secretion was affected. We further demonstrated that the percentage of viable macrophages increased on exposure to a-PVA-SPION. This effect was even stronger when a-PVA-SPION were added very early in the differentiation process. Additionally, transmission electron microscopy analysis revealed that both monocytes and macrophages are able to endocytose a-PVA-SPION. Our findings demonstrate an interaction between human immune cells and a-PVA-SPION which needs to be taken into account when considering the use of a-PVA-SPION in human medicine.

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“…In contrast, the therapeutic targeting of macrophages is relatively easy and specific. 32,33 AuNP is an ideal material for nucleic acid delivery. 14,15 The AuNPs that are coated with nucleotide acids are recruited to the scavenger receptors on the cells, especially the macrophages, facilitating phagocytosis, which is responsible for efficient and superior delivery.…”

Section: Discussionmentioning

confidence: 99%

Gold nanoparticle-based miR155 antagonist macrophage delivery restores the cardiac function in ovariectomized diabetic mouse model

Jia

Chen

Wei

et al. 2017

IJN

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Diabetic cardiomyopathy is a common disease in postmenopausal women, in whom the estrogen deficiency aggravates the pathology. In this study, we have found that estrogen deficiency due to ovariectomy aggravates the inflammation in the hearts of diabetic mice, as depicted by excessive proinflammatory type 1 macrophages (M1) over anti-inflammatory type 2 macrophages (M2). Accordingly, an additional increase of reactive oxygen species, cell apoptosis, cardiac hypertrophy, and fibrosis was observed in the hearts of ovariectomized diabetic mice, in comparison with the diabetes-only group. Significantly, miR155, a potent promoter of M1 polarization, was found to be additionally enhanced in the macrophages and hearts by ovariectomy. Tail vein injection of miR155-AuNP, in which thiol-modified antago-miR155 was covalently conjugated with gold nanoparticle (AuNP), preferentially delivered the nucleic acids into the macrophages via phagocytosis. Together with the increased M2 ratio and reduced inflammation, in vivo delivery of antago-miR155 reduced cell apoptosis and restored the cardiac function. The restoration efficacy of miR155-AuNP was much better than general macrophage depletion by clodrosome. In summary, we revealed that M1/M2 imbalance contributes to the aggravated cardiomyopathy in ovariectomized diabetic mice, and therapeutically reducing miR155 in macrophages by AuNP serves as a promising strategy in improving cardiac function.

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Monocytes and macrophages as nanomedicinal targets for improved diagnosis and treatment of disease

Cited by 92 publications

References 111 publications

Lipopolysaccharide-induced inflammation in monocytes/macrophages is blocked by liposomal delivery of G<sub>i</sub>-protein inhibitor

Lipopolysaccharide-induced inflammation in monocytes/macrophages is blocked by liposomal delivery of G<sub>i</sub>-protein inhibitor

Effects of PVA coated nanoparticles on human immune cells

Gold nanoparticle-based miR155 antagonist macrophage delivery restores the cardiac function in ovariectomized diabetic mouse model

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