Silver Ion Incorporation and Nanoparticle Formation inside the Cavity of <i>Pyrococcus furiosus</i> Ferritin: Structural and Size-Distribution Analyses

Kasyutich, O. I.; Ilari, Andrea; Fiorillo, Annarita; Tatchev, Dragomir; Hoell, Armin; Ceci, Pierpaolo

doi:10.1021/ja910918b

Cited by 108 publications

(97 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Silver or gold contents were quantified as previously described [11] using graphite furnace atomic absorption spectrometry (GFAAS) and the Zeeman effect for the background correction. Protein content was quantified by a previously reported procedure [29].…”

Section: Metal-containing Nanocarrier Preparationmentioning

confidence: 99%

“…Notably, Fts are physiological materials, very soluble in aqueous solutions and in the blood, with low toxicity, susceptible to chemical modifications and being modified by molecular biology techniques [3][4][5][6][7][8][9][10]. Materials such as Fe 3 O 4 , Co 3 O 4 , Mn 3 O 4 , Pt, CoPt, Pd, CdS, CdSe, ZnSe, CaCO 3 , SrCO 3 , Au, Ag and BaCO 3 have been produced and characterized in different ferritin templates [11].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Use of Ferritin-Based Metal-Encapsulated Nanocarriers as Anticancer Agents

et al. 2017

Self Cite

View full text Add to dashboard Cite

Abstract:The ability of ferritin to bind and deliver metals and metal-based drugs to human neuroblastoma SH-SY5Y cells was studied. We used heavy chain (H) ferritin-based metal-containing nanocarriers to test whether these constructs, which are able to cross the blood-brain barrier, may be used for the delivery of toxic molecules to brain cells, and to study their effect on the viability and cellular redox homeostasis of human neuroblastoma cells. We show that metal-containing nanocarriers are efficiently captured by SH-SY5Y cells. Iron-containing nanocarriers have a proliferative effect, while silver and cisplatin-encapsulated nanocarriers determine concentration-dependent neuroblastoma cell death. This work is a proof of concept for the use of ferritins for the delivery of toxic molecules to brain tumors.

show abstract

Section: Metal-containing Nanocarrier Preparationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Use of Ferritin-Based Metal-Encapsulated Nanocarriers as Anticancer Agents

et al. 2017

Self Cite

View full text Add to dashboard Cite

show abstract

“…12 Recently, our group demonstrated the ability of Pyrococcus furiosus ferritin (PfFt) to act as a protein template for the production of Ag(0) nanoparticles encapsulated by ferritin molecules (AgNPs). 13 The AgNPs are characterized by a narrow size distribution (2.1 ( 0.4 nm), high stability in water solution at millimolar particle concentrations, and high thermal stability. The high solubility and stability in water are two essential properties of the silver nanoparticles (NPs), to make them suitable for biomedical applications.…”

mentioning

confidence: 99%

“…Conversely, other AgNPs with adequate solution stability could be obtained only at submicromolar levels. 13 Further, PfFt is a suitable carrier for antileishmanial drugs, since ferritins are known to be phagocitized by macrophages, where the amastigotes proliferate, thereby guaranteeing a high concentration of the encapsulated cargo inside the target cell. 15 The AgNPs induced a potent dose-dependent antiproliferative effect on L. infantum promastigotes, the extracellular Leishmania stage.…”

mentioning

confidence: 99%

Inhibitory Effect of Silver Nanoparticles on Trypanothione Reductase Activity and Leishmania infantum Proliferation

Baiocco

Ilari

Ceci

et al. 2010

ACS Med. Chem. Lett.

Self Cite

103

View full text Add to dashboard Cite

ABSTRACT:In Leishmania the glutathione/glutathione reductase eukaryotic redox system is replaced by the unique trypanothione/trypanothione reductase (TR) system. In vitro, silver is a more effective TR inhibitor than antimony, the first line drug against leishmaniasis in most endemic countries, and its mechanism of inhibition is similar to that of Sb(III). In particular, silver binds with high affinity to the catalytic triad Cys52, Cys57, and His461 0 , thereby inhibiting TR. Here, Ag(0) activity was tested on the promastigote and amastigote stages of Leishmania infantum using a drug-delivery system consisting in Ag(0) nanoparticles encapsulated by ferritin molecules (PfFt-AgNPs). These were able to induce an antiproliferative effect on the parasites at metal concentrations lower than those used with antimony.KEYWORDS: Trypanothione reductase, Leishmania, silver, nanoparticles, drug delivery L eishmaniasis affects at present 12 million people worldwide. 1Because effective vaccines are not yet available, the chemotherapy remains the only treatment option for controlling the infection. Except for the recent encouraging advances in chemotherapy obtained with amphotericin B and its new liposomal formulations, miltefosine and paromomycin, the treatment modalities for leishmaniasis infections mostly rely on antimony-based drugs, which date back over 60 years and suffer from poor efficacy, high toxicity, and increasing resistance. 2 The Leishmania life cycle involves two principal morphological stages, promastigote and amastigote. The first one develops within an insect vector, a phlebotomine sand-fly; the second one infects the macrophages of vertebrate hosts, which produce considerable amounts of H 2 O 2 to eliminate intruding parasites. The search for urgently needed drugs against Leishmania parasites is focusing on metabolic pathways vital for the amastigote parasite and distinct from the analogous metabolism in the mammalian host. In this respect, the trypanothione metabolism enzymes are considered as promising targets of new drugs against leishmaniasis.The trypanothione (T(SH) 2 ) is synthesized from glutathione and spermidine by the trypanothione synthetase (TryS) and is kept reduced by the trypanothione reductase (TR). Trypanothione participates in crucial thiol-disulfide exchange reactions and serves as electron donor in several metabolic pathways, from synthesis of DNA precursors to oxidant detoxification. The T(SH) 2 /TR system replaces many of the antioxidant and metabolic functions of the glutathione/glutathione reductase (GR) and thioredoxin/thioredoxin reductase (TrxR) systems present in other organisms and therefore is necessary for the parasite survival. 3-5 Sb(V), reduced inside the amastigote to Sb(III), 6 interferes in vivo with the T(SH) 2 metabolism by inducing rapid efflux of intracellular T(SH) 2 and inhibiting TR in intact cells. 7

show abstract

“…As a consequence, ferritin proteins guarantee excellent size and shape control in metal nanoparticle synthesis, and several materials, such as Fe 3 O 4 , Co 3 O 4 , Mn 3 O 4 , Pt, CoPt, Pd, CdS, CdSe, ZnSe, CaCO 3 , Ag, and Au have been produced within the internal cavity of ferritin proteins. [10][11][12][13][14][15][16][17][18] The small size of ferritins (,20 nm) increases the chances of larger nanoparticles passing human body barriers and reaching specific targets. Indeed, the dimensions of the nanoparticles, which must be small enough to penetrate capillary fenestrations and large enough to avoid rapid clearance through the kidney (the ideal diameter being lower than 50-60 nm and greater than 6-8 nm, respectively), 19,20 are one of the key prerequisites for efficient targeted delivery, together with a long-circulating capability of the carrier and high specificity of the selector towards the target receptor.…”

mentioning

confidence: 99%

Selective targeting of melanoma by PEG-masked protein-based multifunctional nanoparticles

Vannucci¹,

Falvo²,

Fornara³

et al. 2012

IJN

Self Cite

View full text Add to dashboard Cite

Background: Nanoparticle-based systems are promising for the development of imaging and therapeutic agents. The main advantage of nanoparticles over traditional systems lies in the possibility of loading multiple functionalities onto a single molecule, which are useful for therapeutic and/or diagnostic purposes. These functionalities include targeting moieties which are able to recognize receptors overexpressed by specific cells and tissues. However, targeted delivery of nanoparticles requires an accurate system design. We present here a rationally designed, genetically engineered, and chemically modified protein-based nanoplatform for cell/tissue-specific targeting. Methods: Our nanoparticle constructs were based on the heavy chain of the human protein ferritin (HFt), a highly symmetrical assembly of 24 subunits enclosing a hollow cavity. HFt-based nanoparticles were produced using both genetic engineering and chemical functionalization methods to impart several functionalities, ie, the α-melanocyte-stimulating hormone peptide as a melanoma-targeting moiety, stabilizing and HFt-masking polyethylene glycol molecules, rhodamine fluorophores, and magnetic resonance imaging agents. The constructs produced were extensively characterized by a number of physicochemical techniques, and assayed for selective melanoma-targeting in vitro and in vivo. Results: Our HFt-based nanoparticle constructs functionalized with the α-melanocytestimulating hormone peptide moiety and polyethylene glycol molecules were specifically taken up by melanoma cells but not by other cancer cell types in vitro. Moreover, experiments in melanoma-bearing mice indicate that these constructs have an excellent tumor-targeting profile and a long circulation time in vivo. Conclusion: By masking human HFt with polyethylene glycol and targeting it with an α-melanocyte-stimulating hormone peptide, we developed an HFt-based melanoma-targeting nanoplatform for application in melanoma diagnosis and treatment. These results could be of general interest, because the same strategy can be exploited to develop ad hoc nanoplatforms for specific delivery towards any cell/tissue type for which a suitable targeting moiety is available. Keywords: multifunctional nanoparticles, ferritin, nanoplatform, cancer-targeting, melanoma IntroductionDevelopment of multifunctional nanoparticles for nanomedicine applications, such as cell/tissue-specific delivery, biomedical imaging and therapy, has recently gained wide popularity. [1][2][3][4] Various types of materials, including synthetic polymers and lipids, have been increasingly utilized as platforms for nanoparticle synthesis. 1,5 Despite the large number of bioconjugation techniques available, the attainment of multifunctional nanoprobes endowed with desired bioactivity, targeting specificity, and stability remains a challenge. Approaches using protein-cage structures, such as proteins belonging to the ferritin family, are novel and very promising. 6,7 Apoferritin is a highly symmetrical multimeric protein consisting of 2...

show abstract

Silver Ion Incorporation and Nanoparticle Formation inside the Cavity of Pyrococcus furiosus Ferritin: Structural and Size-Distribution Analyses

Cited by 108 publications

References 50 publications

Use of Ferritin-Based Metal-Encapsulated Nanocarriers as Anticancer Agents

Use of Ferritin-Based Metal-Encapsulated Nanocarriers as Anticancer Agents

Inhibitory Effect of Silver Nanoparticles on Trypanothione Reductase Activity and Leishmania infantum Proliferation

Selective targeting of melanoma by PEG-masked protein-based multifunctional nanoparticles

Contact Info

Product

Resources

About