Clusterin in the protein corona plays a key role in the stealth effect of nanoparticles against phagocytes

Aoyama, Michihiko; Hata, Katsutomo; Higashisaka, Kazuma; Nagano, Kazuya; Yoshioka, Yasuo; Tsutsumi, Yasuo

doi:10.1016/j.bbrc.2016.10.121

Cited by 65 publications

(45 citation statements)

References 23 publications

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“…It has been hypothesized that clusterin adhesion on the surfaces of PEGylated nanoparticles induces a stealth effect and inhibits nanoparticle uptake by phagocytes. 70 Thus, immunotoxicity can be mitigated or augmented depending on the types of nanoparticles and adsorbed plasma proteins. 71 Here, analyzing the protein corona of four different nanoparticle compositions demonstrated the importance of investigating nano-bio interfaces at nanoparticle surfaces, which will enable choices of delivery vehicles depending on the targeting application and experimental design.…”

Section: Resultsmentioning

confidence: 99%

Polyserotonin Nanoparticles as Multifunctional Materials for Biomedical Applications

et al. 2018

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Serotonin-based nanoparticles represent a class of previously unexplored multifunctional nanoplatforms with potential biomedical applications. Serotonin, under basic conditions, self-assembles into monodisperse nanoparticles via autoxidation of serotonin monomers. To demonstrate potential applications of polyserotonin nanoparticles for cancer therapeutics, we show that these particles are biocompatible, exhibit photothermal effects when exposed to near-infrared radiation, and load the chemotherapeutic drug doxorubicin releasing it contextually and responsively in specific microenvironments. Quantum mechanical and molecular dynamics simulations were performed to interrogate the interactions between surface-adsorbed drug molecules and polyserotonin nanoparticles. To investigate the potential of polyserotonin nanoparticles for in vivo targeting, we explored their nano-bio interfaces by conducting protein corona experiments. Polyserotonin nanoparticles had reduced surface-protein interactions under biological conditions compared to polydopamine nanoparticles, a similar polymer material widely investigated for related applications. These findings suggest that serotonin-based nanoparticles have advantages as drug-delivery platforms for synergistic chemo- and photothermal therapy associated with limited nonspecific interactions.

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Section: Resultsmentioning

confidence: 99%

Polyserotonin Nanoparticles as Multifunctional Materials for Biomedical Applications

et al. 2018

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“…MDM2 reactivated p53 via polyubiquitylation and inhibited its transcriptional activity [43]. Another study demonstrated that SIRT2 deacetylated p53 and inhibited its transcriptional activity [44]. However, the relationship between SIRT2 and MDM2 is not clear.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of SIRT2 Alleviates Fibroblast Activation and Renal Tubulointerstitial Fibrosis via MDM2

You

Wang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Renal tubular epithelial cells and fibroblasts are the main sources of myofibroblasts, and these cells produce the extracellular matrix during tubulointerstitial fibrosis (TIF). Histone deacetylases (HDAC) inhibitors exert an antifibrogenic effect in the skin, liver and lung. Sirtuin 2 (SIRT2), which is a class III HDAC, is an important member of NAD⁺-dependent protein deacetylases. The current study evaluated the role of SIRT2 in renal TIF. Methods: Immunohistochemical staining and Western blot were performed to evaluate SIRT2 expression in TIF patients and unilateral urethral obstruction (UUO) mice. Western blot was used to assess the protein levels of SIRT2, α-SMA, collagen III, fibronectin, and MDM2 in tubular epithelial cells and fibroblasts. The specific inhibitor AGK2 was used to inhibit SIRT2 activity, and targeted siRNA was used to suppress SIRT2 expression. Results: SIRT2 expression increased in the tubulointerstitium of TIF patients and UUO mice. SIRT2 inhibition ameliorated TIF in UUO mice. SIRT2 expression in tubular cells was unchanged after exposure to TGF-β1. The SIRT2-specifc inhibitor AGK2 did not attenuate TGF-β1-induced tubular epithelial-mesenchymal transition. However, SIRT2 was upregulated in fibroblasts, and fibroblasts were activated after TGF-β1 treatment. Genetic knockdown and chemical inhibition of SIRT2 attenuated TGF-β1-induced fibroblast activation. We also explored the downstream signaling of SIRT2 during fibroblast activation. Genetic knockdown and chemical inhibition of SIRT2 suppressed TGF-β1-induced increase in MDM2 expression, and inhibition of the MDM2-p53 interaction using Nutlin-3 did not suppress SIRT2 upregulation. Conclusion: Our results suggest that SIRT2 participates in the activation of fibroblasts and TIF, which is mediated via regulation of the MDM2 pathway, and the downregulation of SIRT2 may be a therapeutic strategy for renal fibrosis.

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“…Nowadays, it is accepted that once nanoparticles are incubated in biological fluids such as blood, they will be covered by proteins [41]. Not only do these proteins interact with the chemical coatings of materials, but they mostly also modulate their biological fate [28,42].…”

Section: Importance Of the Protein Corona On Biological Interactions mentioning

confidence: 99%

Toxicological Risk Assessment of Emerging Nanomaterials: Cytotoxicity, Cellular Uptake, Effects on Biogenesis and Cell Organelle Activity, Acute Toxicity and Biodistribution of Oxide Nanoparticles

Maurizi¹,

Papa²,

Boudon³

et al. 2018

Unraveling the Safety Profile of Nanoscale Particles and Materials - From Biomedical to Environmental Applications

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The lack of toxicological data on nanomaterials makes it difficult to assess the risk related to their exposure, and as a result further investigation is required. This chapter presents the synthesis of controlled oxide nanoparticles followed by the evaluation of their safety profile or toxicity (iron, titanium and zinc oxides). The controlled surface chemistry, dispersion in several media, morphology and surface charge of these nanoparticles are presented (transmission electron microscopy, dynamic light scattering, zeta potential, X-ray photoelectron spectroscopy). Classical cytotoxic and cellular uptake studies on different cancer cell lines from liver, prostate, heart, brain and spinal cord are discussed. The incidence of nanoparticles on biogenesis and activity of cell organelles is also highlighted, as well as their biodistribution in animal models. The acute toxicity on zebrafish embryo model is also presented. Finally, the stress is put on the influence and the necessity of controlling the protein corona, a layer of plasma proteins physically adsorbed at the surface of such nanoparticles as a result of their presence in the bloodstream (or relevant biological fluids).

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Clusterin in the protein corona plays a key role in the stealth effect of nanoparticles against phagocytes

Cited by 65 publications

References 23 publications

Polyserotonin Nanoparticles as Multifunctional Materials for Biomedical Applications

Polyserotonin Nanoparticles as Multifunctional Materials for Biomedical Applications

Inhibition of SIRT2 Alleviates Fibroblast Activation and Renal Tubulointerstitial Fibrosis via MDM2

Toxicological Risk Assessment of Emerging Nanomaterials: Cytotoxicity, Cellular Uptake, Effects on Biogenesis and Cell Organelle Activity, Acute Toxicity and Biodistribution of Oxide Nanoparticles

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