Hyaluronan Nanoparticles Selectively Target Plaque-Associated Macrophages and Improve Plaque Stability in Atherosclerosis

Beldman, Thijs J.; Senders, Max L.; Alaarg, Amr; Pérez-Medina, Carlos; Tang, Jun; Zhao, Yiming; Fay, François; Deichmöller, Jacqueline; Born, Benjamin; Desclos, Emilie; Wel, Nicole N. van der; Hoebe, Ron A.; Kohen, Förtüne; Kartvelishvily, Elena; Neeman, Michal; Reiner, Thomas; Calcagno, Claudia; Fayad, Zahi A.; Winther, Menno P.J. de; Lutgens, Esther; Mulder, Willem J. M.; Kluza, Ewelina

doi:10.1021/acsnano.7b01385

Cited by 157 publications

(151 citation statements)

References 83 publications

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“…The presence of HA greatly decreased their uptake by the liver and, as recently described in another study on hyaluronan nanoparticles [5] selectively enhanced the plaque accumulation. Taking into consideration the efficient plaque macrophage-targeting mechanism, the cholesterol efflux-inducing capacity and the anti-atherosclerotic potential of ST-HA-PLGA-rHDL, effective local therapy of atherosclerotic plaque can be envisioned.…”

Section: Targeted Delivery Of Simvastatin For Local Atherosclerotic Psupporting

confidence: 71%

Treat Or Track: Nanoagents in the Service of Health

Lyer

Janko

Friedrich

et al. 2017

Nanomedicine (Lond.)

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Atherosclerosis is the most common cause of death worldwide. However, although considerable progress has been achieved in understanding, diagnosis and treatment of atherosclerosis, some important parts of the puzzle still remain unknown.In their paper, Stein-Merlob et al. aimed to test the hypothesis that atherosclerotic plaques predisposed to thrombosis display an abnormal permeability and, second, that these thrombosis-prone areas are characterized by a high cell density. To answer these questions, the authors induced atherosclerotic plaques in 31 rabbits by balloon injury and 8 weeks of western diet (i.e., chow with 1% cholesterol) followed by 4 weeks of normal chow. To assess the impaired barrier function of the plaque endothelium, ultrasmall superparamagnetic iron oxide nanoparticles (CLIO) were synthesized and coated with dextran, followed by crosslinking and functionalization with a near infrared probe CyAm7 (unfortunately, no size or reference is given). At the end of the nutrition scheme, 21 animals received 2.5 mg/kg CLIO-CyAm7 and 3 received saline. After further 24 h, 9 animals were sacrificed and 15 received pharmacological trigger consisting of Russell viper venom and histamine to induce plaque thrombosis. The remaining 7 animals were administered Evans Blue in addition to 5 mg/kg CLIO-CyAm7, to assess whether endothelial barrier function was impaired. The animals underwent in vivo intravascular near-infrared fluorescence imaging (NIRF) and/or intravascular ultrasound, followed by ex vivo NIRF and histological analyses of the representative artery sections.The results showed that the nanoparticles accumulated at the densely cellularized luminal surface of the plaques, but also appeared in deeper parts (33%), if neovascularization was observable. Co-staining with Evans Blue revealed a good correlation between the dye penetration and the fluorescence signal of the CLIOs, which led the authors to the conclusion that the particles mainly accumulated in the areas of higher endothelial permeability. Histological analysis showed that the nanoparticles were taken up not only by macrophages, but also by endothelial and smooth muscle cells, although no numeric distribution was given in the paper. In 10 out of 15 animals, plaque-adherent thrombi were detected after pharmacological triggering and a quantitative analysis showed that the areas with such thrombi showed higher nanoparticle signals than those, which were thrombus-negative. Finally, intravascular NIRF and ultrasound showed a good correlation between CLIO-signal and the occurrence of plaque-adherent thrombi after pharmacological triggering.The authors conclude that the used nanoparticles accumulate preferentially in plaque areas with impaired barrier function and increased surface cellularity, and that those areas are prone to plaque thrombosis. Since the accumulation of iron oxide-based nanoparticles in these areas can also be visualized by magnetic resonance imaging,

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Section: Targeted Delivery Of Simvastatin For Local Atherosclerotic Psupporting

confidence: 71%

Treat Or Track: Nanoagents in the Service of Health

Lyer

Janko

Friedrich

et al. 2017

Nanomedicine (Lond.)

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“…[295] The polymerized HA was associated with phagocytosis inhibition and anti-inflammatory effects, contrary to angiogenesis and inflammation-stimulatory ability of low-molecular weight HA. In order to alleviate atherosclerosis-associated inflammation, polymerized HA NPs were prepared for specific targeting through interacting with receptors, such as CD44 and TLR4 expressed on macrophages.…”

Section: Modulation Of Macrophagesmentioning

confidence: 97%

“…On the contrary, M2 is a prohealing phenotype that assists in anti-inflammation process and tissue repair by enhancing the secretion of IL-10, TGF-β, and VEGF. [44,295,311,312] Activated macrophages are reckoned to participate in the inflammation and pathogenesis of RA. [310] Many nanoparticle platforms have been developed to reduce proinflammatory macrophages or regulate macrophage polarization for treatment of dysfunctional macrophage-associated diseases.…”

Section: Modulation Of Macrophagesmentioning

confidence: 99%

“…2019, 6,1900101 HA-NP CD44 and TLR4 on macrophages - [295] Dextran-dexamethasone prodrug Lectin and scavenger receptor on macrophages Esterase [44] Au NP IL-4 -- [296] MSNP IL-4 -- [297] MTC cross-linked with miRNA-146b Mannose receptor on BMDMs - [298] Silica nanoparticle conjugated with KGM -Mannose receptor on BMDMs - [299] RGD-coated Au NP protected by a magnetic nanocage -- [300] Modulation of Tregs Au NP Hyperforin -- [301] Au NP Hexapeptide -- [302] PLGA NP Protein or peptide antigens and rapamycin -- [303] PLA-PLGA NP PLP and rapamycin -- [304] Porous silicon nanoparticle Rapamycin and OVA peptide CD11c on DCs - [36] PLGA NP Anti-CD3 Ab PNAd on HEV - [42] PLGA NP Diabetogenic peptide -- [305] Iron oxide nanoparticle T1D-relevant peptide-MHC class I complexe -- [306] Iron oxide nanoparticle Diabetogenic antigen peptide-MHC class II complex -- [307] PLGA NP IL-2 and TGF-β Biotin on CD4+ T cells - [308] Obesity increases the M1 macrophage infiltration in adipose tissue and promotes the secretion of pro-inflammatory cytokines, such as TNF-α and IL-6, which lead to high risk of glucose intolerance and insulin resistance. Sci.…”

Section: Modulation Of Macrophagesmentioning

confidence: 99%

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Immunomodulatory Nanosystems

et al. 2019

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Immunotherapy has emerged as an effective strategy for the prevention and treatment of a variety of diseases, including cancer, infectious diseases, inflammatory diseases, and autoimmune diseases. Immunomodulatory nanosystems can readily improve the therapeutic effects and simultaneously overcome many obstacles facing the treatment method, such as inadequate immune stimulation, off‐target side effects, and bioactivity loss of immune agents during circulation. In recent years, researchers have continuously developed nanomaterials with new structures, properties, and functions. This Review provides the most recent advances of nanotechnology for immunostimulation and immunosuppression. In cancer immunotherapy, nanosystems play an essential role in immune cell activation and tumor microenvironment modulation, as well as combination with other antitumor approaches. In infectious diseases, many encouraging outcomes from using nanomaterial vaccines against viral and bacterial infections have been reported. In addition, nanoparticles also potentiate the effects of immunosuppressive immune cells for the treatment of inflammatory and autoimmune diseases. Finally, the challenges and prospects of applying nanotechnology to modulate immunotherapy are discussed.

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Section: Preclinical Biomedical Applicationsmentioning

confidence: 99%

Recent Advances in Managing Atherosclerosis via Nanomedicine

Chan

Zhang

Cheng

et al. 2017

Small

102

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Atherosclerosis, driven by chronic inflammation of the arteries and lipid accumulation on the blood vessel wall, underpins many cardiovascular diseases with high mortality rates globally, such as stroke and ischemic heart disease. Engineered bio-nanomaterials are now under active investigation as carriers of therapeutic and/or imaging agents to atherosclerotic plaques. This Review summarizes the latest bio-nanomaterial-based strategies for managing atherosclerosis published over the past five years, a period marked by a rapid surge in preclinical applications of bio-nanomaterials for imaging and/or treating atherosclerosis. To start, the biomarkers exploited by emerging bio-nanomaterials for targeting various components of atherosclerotic plaques are outlined. In addition, recent efforts to rationally design and screen for bio-nanomaterials with the optimal physicochemical properties for targeting plaques are presented. Moreover, the latest preclinical applications of bio-nanomaterials as carriers of imaging, therapeutic, or theranostic agents to atherosclerotic plaques are discussed. Finally, a mechanistic understanding of the interactions between bio-nanomaterials and the plaque ("athero-nano" interactions) is suggested, the opportunities and challenges in the clinical translation of bio-nanomaterials for managing atherosclerosis are discussed, and recent clinical trials for atherosclerotic nanomedicines are introduced.

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Hyaluronan Nanoparticles Selectively Target Plaque-Associated Macrophages and Improve Plaque Stability in Atherosclerosis

Cited by 157 publications

References 83 publications

Treat Or Track: Nanoagents in the Service of Health

Treat Or Track: Nanoagents in the Service of Health

Immunomodulatory Nanosystems

Recent Advances in Managing Atherosclerosis via Nanomedicine

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