Gold and silver nanoparticles conjugated with heparin derivative possess anti-angiogenesis properties

Kemp, Melissa M.; Kumar, Ashavani; Mousa, Shaymaa S; Dyskin, Evgeny; Yalçın, Murat; Ajayan, Pulickel M.; Linhardt, Robert J.; Mousa, Shaker A.

doi:10.1088/0957-4484/20/45/455104

Cited by 145 publications

(104 citation statements)

References 36 publications

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“…Previous studies have shown that gold nanoparticles (AuNPs) can affect vascular endothelial growth factor (VEGF)-and basic fibroblast growth factor (bFGF)-induced cell proliferation in vitro and angiogenesis in vivo. 16,17 In addition, AuNPs bind to VEGF in arthritic synovial fluid, exert antiangiogenic activities, and reduce inflammation and arthritis. 18 However, some studies have also shown that nanoparticles, particularly high concentrations of silver nanoparticles, exhibit cell cytotoxicity and, therefore, induce HO-1 expression.…”

mentioning

confidence: 99%

Gold nanoparticles induce heme oxygenase-1 expression through Nrf2 activation and Bach1 export in human vascular endothelial cells

Lai¹,

Shieh²,

Tsou³

et al. 2015

IJN

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It has been reported that increased levels and activity of the heme oxygenase-1 (HO-1) protein ameliorate tissue injuries. In the present study, we investigated the effects and mechanisms of action of gold nanoparticles (AuNPs) on HO-1 protein expression in human vascular endothelial cells (ECs). The AuNPs induced HO-1 protein and mRNA expression in a concentration- and time-dependent manner. The induction was reduced by the thiol-containing antioxidants, including N-acetylcysteine and glutathione, but not by the non-thiol-containing antioxidants and inhibitors that block the enzymes for intracellular reactive oxygen species generation. The AuNPs enhanced Nrf2 protein levels but did not affect Nrf2 mRNA expression. In response to the AuNP treatment, the cytosolic Nrf2 translocated to the nucleus, and, concomitantly, Bach1 exited the nucleus and its tyrosine phosphorylation increased. The chromatin immunoprecipitation assay revealed that the translocated Nrf2 bound to the antioxidant-response element located in the E2 enhancer region of the HO-1 gene promoter and acted as a transcription factor. Although N-acetylcysteine inhibited the AuNP-induced Nrf2 nuclear translocation, the AuNPs did not promote intracellular reactive oxygen species production or endoplasmic reticulum stress in the ECs. Knockdown of Nrf2 expression by RNA interference significantly inhibited AuNP-induced HO-1 expression at the protein and mRNA levels. In summary, AuNPs enhance the levels and nuclear translocation of the Nrf2 protein and Bach1 export/tyrosine phosphorylation, leading to Nrf2 binding to the HO-1 E2 enhancer promoter region to drive HO-1 expression in ECs. This study, together with our parallel findings, demonstrates that AuNPs can act as an HO-1 inducer, which may partially contribute to their anti-inflammatory bioactivity in human vascular ECs.

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mentioning

confidence: 99%

Gold nanoparticles induce heme oxygenase-1 expression through Nrf2 activation and Bach1 export in human vascular endothelial cells

Lai¹,

Shieh²,

Tsou³

et al. 2015

IJN

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“…34 Furthermore, addition of a sulfated oligosaccharide enhances angiogenesis and stabilizes the capillary network of new blood vessels. 10,35 Thus, a properly developed system of blood vessels of the correct diameter may decrease the resistance of peripheral vessels and, consequently, slightly decrease the force of heart contractions, leading to a proper heart weight. It should also be noted that the activity of alanine aminotransferase, aspartate aminotransferase, and other biochemical parameters of blood did not change, which otherwise could be the sign of distortion in the homeostasis of the organism, including the circulatory system.…”

Section: Discussionmentioning

confidence: 99%

“…9 The genetic capacity for proper development of muscle tissue in embryos of animals and humans may be hampered by a shortage of sulfur signaling compounds in the extracellular matrix, especially glycosaminoglycans. 10 The unique properties of gold nanoparticles (nano-Au) are due to their small size, much larger surface area per unit mass compared with larger particles, and a greater proportion of atoms exposed on the surface of the particles, making them much more reactive than larger particles. 11 Nano-Au exhibit a strong affinity for thiol groups, which allows efficient and selective bonding with intracellular compounds.…”

Section: Introductionmentioning

confidence: 99%

Effect of heparan sulfate and gold nanoparticles on muscle development during embryogenesis

Zielińska¹,

Sawosz²,

Grodzik³

et al. 2011

IJN

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Purpose It was hypothesized that heparan sulfate (HS) as an essential compound for myogenesis and nanoparticles of gold (nano-Au) as highly reactive compounds can affect muscle development as a consequence of molecular regulation of muscle cell formation, and that these effects may be enhanced by a complex of HS conjugated with nano-Au. The objective of the present study was to determine the effect of administration of nano-Au, HS, and a nano-Au+HS complex on the morphological and molecular characteristics of breast muscle during embryogenesis. Methods Chicken embryos were used as in vivo model. Fertilized chicken eggs (n = 350) were randomly divided into the control group and the groups treated with nano-Au, HS, and nano-Au+HS. The experimental solutions were given in ovo on the first day of incubation and the embryos were evaluated on day 20 of incubation. The methods included biochemical indices in blood, immunohistochemistry, microscopy (transmission electron microscopy, scanning electron microscopy, confocal), and gene expression at the messenger ribonucleic acid and protein levels. Results The treatments did not adversely affect mortality, organ weight, and homeostasis of the embryos. HS stimulated the development and maturation of breast muscle by increasing the number of nuclei, satellite cells, and muscle fibers and affected the expression of basic fibroblast growth factor-2 and paired-box transcription factor-7. Furthermore, the nano-Au+HS complex contributed to the increased number of myocytes and nuclei in chicken embryo muscles. Conclusion The results indicate that the administration of HS and nano-Au affects muscle development and that this effect is enhanced by conjugating HS with nano-Au.

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“…The folate-conjugated heparin-taxol nanoparticles were more efficiently taken up by folate receptor overexpressing cancer cells compared with folate receptor-deficient cell lines. Heparin has also been conjugated with chitosan (47), gold (48), and iron oxide nanoparticles (49). Moreover, heparinbased co-polymers have been used to develop multifunctional nanoparticle systems for anti-cancer drug delivery.…”

Section: Nanoparticle Platforms: Emerging Translational Nanodrug Delimentioning

confidence: 99%

Nanodrug Delivery Systems: A Promising Technology for Detection, Diagnosis, and Treatment of Cancer

et al. 2014

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Abstract. Nanotechnology has enabled the development of novel therapeutic and diagnostic strategies, such as advances in targeted drug delivery systems, versatile molecular imaging modalities, stimulus responsive components for fabrication, and potential theranostic agents in cancer therapy. Nanoparticle modifications such as conjugation with polyethylene glycol have been used to increase the duration of nanoparticles in blood circulation and reduce renal clearance rates. Such modifications to nanoparticle fabrication are the initial steps toward clinical translation of nanoparticles. Additionally, the development of targeted drug delivery systems has substantially contributed to the therapeutic efficacy of anti-cancer drugs and cancer gene therapies compared with nontargeted conventional delivery systems. Although multifunctional nanoparticles offer numerous advantages, their complex nature imparts challenges in reproducibility and concerns of toxicity. A thorough understanding of the biological behavior of nanoparticle systems is strongly warranted prior to testing such systems in a clinical setting. Translation of novel nanodrug delivery systems from the bench to the bedside will require a collective approach. The present review focuses on recent research efforts citing relevant examples of advanced nanodrug delivery and imaging systems developed for cancer therapy. Additionally, this review highlights the newest technologies such as microfluidics and biomimetics that can aid in the development and speedy translation of nanodrug delivery systems to the clinic.

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Gold and silver nanoparticles conjugated with heparin derivative possess anti-angiogenesis properties

Cited by 145 publications

References 36 publications

Gold nanoparticles induce heme oxygenase-1 expression through Nrf2 activation and Bach1 export in human vascular endothelial cells

Gold nanoparticles induce heme oxygenase-1 expression through Nrf2 activation and Bach1 export in human vascular endothelial cells

Effect of heparan sulfate and gold nanoparticles on muscle development during embryogenesis

Nanodrug Delivery Systems: A Promising Technology for Detection, Diagnosis, and Treatment of Cancer

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