&lt;p&gt;Distinct Proteins in Protein Corona of Nanoparticles Represent a Promising Venue for Endogenous Targeting – Part II: In vitro and in vivo Kinetics Study&lt;/p&gt;

Sebak, Aya; Gomaa, Iman; ElMeshad, Aliaa Nabil; Farag, Mahmoud Hussien; Breitinger, Hans‐Georg; Abdel‐Kader, Mahmoud H.

doi:10.2147/ijn.s273721

Cited by 16 publications

(14 citation statements)

References 95 publications

(186 reference statements)

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“…Endocytosis and exocytosis of AgNP occur simultaneously and depend on physicochemical properties of NP and protein corona [ 32 ]. All nanostructures preferentially accumulate in tumor cells due to the enhanced permeability and retention (EPR) effect.…”

Section: Toxicity Of Nanosilvermentioning

confidence: 99%

“…All nanostructures preferentially accumulate in tumor cells due to the enhanced permeability and retention (EPR) effect. The tumors possess a leaky vasculature and lack lymphatic drainage, allowing the AgNP to reside at the tumor site for a longer duration compared to the free drug molecules [ 32 ]. Cytotoxicity of the nanosilver for tumor cells provides anticancer properties.…”

Section: Toxicity Of Nanosilvermentioning

confidence: 99%

“…The chemical composition of protein corona may serve as a fingerprint for NP of certain types since different NP tend to recruit cellular and serum proteins to variable extents. Vitronectin mediates accumulation in integrin receptor-expressing melanoma cells both in vitro and in vivo, while complement 3 protein (C3), an opsonin and dysopsonin regulate the balance between the reticuloendothelial system uptake and blood circulation [ 32 ].…”

Section: Protection Mechanisms Of Cellular and Host Defense Against Nanosilvermentioning

confidence: 99%

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Silver Nanostructures: Limited Sensitivity of Detection, Toxicity and Anti-Inflammation Effects

Морозова

2021

IJMS

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Nanosilver with sizes 1–100 nm at least in one dimension is widely used due to physicochemical, anti-inflammatory, anti-angiogenesis, antiplatelet, antifungal, anticancer, antibacterial, and antiviral properties. Three modes of the nanosilver action were suggested: “Trojan horse”, inductive, and quantum mechanical. The Ag+ cations have an affinity to thiol, amino, phosphate, and carboxyl groups. Multiple mechanisms of action towards proteins, DNA, and membranes reduce a risk of pathogen resistance but inevitably cause toxicity for cells and organisms. Silver nanoparticles (AgNP) are known to generate two reactive oxygen species (ROS)-superoxide (•O2−) and hydroxyl (•OH) radicals, which inhibit the cellular antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase) and cause mechanical damage of membranes. Ag+ release and replacement by electrolyte ions with potential formation of insoluble AgCl result in NP instability and interactions of heavy metals with nucleic acids and proteins. Protein shells protect AgNP core from oxidation, dissolution, and aggregation, and provide specific interactions with ligands. These nanoconjugates can be used for immunoassays and diagnostics, but the sensitivity is limited at 10 pg and specificity is restricted by binding with protective proteins (immunoglobulins, fibrinogen, albumin, and others). Thus, broad implementation of Ag nanostructures revealed limitations such as instability; binding with major blood proteins; damage of proteins, nucleic acids, and membranes; and immunosuppression of the majority of cytokines.

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Section: Toxicity Of Nanosilvermentioning

confidence: 99%

Section: Toxicity Of Nanosilvermentioning

confidence: 99%

Section: Protection Mechanisms Of Cellular and Host Defense Against Nanosilvermentioning

confidence: 99%

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Silver Nanostructures: Limited Sensitivity of Detection, Toxicity and Anti-Inflammation Effects

Морозова

2021

IJMS

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“…Endocytosis and exocytosis of AgNPs occur simultaneously and depend on physicochemical properties of NPs and protein corona [14]. All nanostructures preferentially accumulate in tumor cells due to the enhanced permeability and retention (EPR) effect.…”

Section: Cytotoxicity Of Ag Ions and Nanoconjugates Of Agnps With Major Blood Proteinsmentioning

confidence: 99%

“…All nanostructures preferentially accumulate in tumor cells due to the enhanced permeability and retention (EPR) effect. The tumors possess a leaky vasculature and lack lymphatic drainage allowing the drug-loaded NPs to reside at the tumor site for a longer duration compared to the free drug molecules [14].…”

Section: Cytotoxicity Of Ag Ions and Nanoconjugates Of Agnps With Major Blood Proteinsmentioning

confidence: 99%

Nanosilver in Biomedicine: Advantages and Restrictions

Морозова¹,

Klinov²

2021

Silver Micro-Nanoparticles - Properties, Synthesis, Characterization, and Applications

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Nanosilver (in a range 1–100 nm) binds with thyol-, amino- and carboxy-groups of aminoacid residues of proteins and nucleic acids, thus providing inactivation of pathogenic multidrug-resistant microorganisms. Besides antibacterial, antiviral, antifungal and anti-cancer properties Ag-based nanomaterials possess anti-inflammatory, anti-angiogenesis and antiplatelet features. Drug efficacy depends on their stability, toxicity and host immune response. Citrate coated Ag nanoparticles (NPs) remain stable colloid solutions in deionized water but not in the presence of ions due to replacement of Ag+ by electrolyte ions, potential formation of insoluble AgCl, subsequent catalyzed oxidative corrosion of Ag and further dissolution of surface layer of Ag2O. Protein shells protect core of AgNPs from oxidation, dissolution, aggregation and provide specific interactions with ligands. These nanoconjugates can be used for immunoassays and diagnostics but the sensitivity threshold does not exceed 10 pg Cytotoxicity of AgNPs conjugated with proteins is associated with the rate of intracellular Ag+ release, a ‘Trojan horse’ effect, and exceeds one of Ag+ because of endocytosis uptake of NPs but not ions. Relatively toxic nanosilver causes immunosuppression of the majority of cytokines with a few exceptions (IL-1β, G-CSF, MCP-1) whereas AgNO3 additionally activate TNFα and IL8 gene expression.

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Nano‐Mediated PDT as a Multifunctional Immunomodulatory Agent in the Intricate Milieu of Melanoma

Sebak,

Abdel‐Halim,

Abdelrahman

et al. 2024

Advanced Therapeutics

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The complexity of the tumor microenvironment (TME) and nutrient competition represent the main causes of therapy resistance in cancers, including malignant melanoma (MM). Photodynamic therapy (PDT), through a cascade of events including its ability to induce significant immune responses, causes tumor eradication. However, the high pigmentation level of melanoma, lack of adequate accumulation of photosensitizers (PSs) in the target tissue as well as their nonspecific toxicity represent three main obstacles to obtaining satisfactory responses in melanoma. To prevail over these challenges, this study employed a depigmentation strategy followed by a nano‐mediated topical application of PDT using a chlorophyllin derivative as PS, focusing on evaluation of the immunomodulatory and metabolic regulatory axes of PDT in melanoma. Photo‐immunomodulation was assessed in a melanoma mouse model using a nanocarrier system of the PS. Markers of the immunosuppressive microenvironment and T cell exhaustion, as independent immune hallmarks, were quantified. The histopathology of spleen and skin/tumor was evaluated. The amino acid profile was quantified from normal skin or tumor biopsies using UHPLC‐MS/MS. Around 80% of the 300 nm transethosomal ferrous chlorophyllin (fC‐TEs) were retained in the tumor over 24 h upon topical application. Arbutin 2% gel not only decreased the melanin content of tumors, but also regulated the expression of interleukin 12 (IL‐12), IL‐10, transforming growth factor beta (TGF‐β) and tumor necrosis factor alpha (TNF‐α). Additionally, the nano‐mediated PDT strategy decreased the expression of programmed cell death protein 1 (PD‐1) & its ligand 1 (PD‐L1) and reduced the activity of arginase 1 (Arg1) through an upregulation of miRNA155. A mild recruitment of megakaryocytes (MKs) was observed in the spleen of the PDT group. This special localization of MKs depicts effector immune properties. Lastly, the combination of PDT and arbutin restored the normal tissue levels of arginine (Arg), glutamine (Gln) and lavished those of tryptophan (Trp). Nano‐mediated PDT represents a novel immunotherapeutic approach in melanoma by a triple modulation of the immune suppressive TME, immune checkpoint signaling, and reprogrammed tumor metabolism.This article is protected by copyright. All rights reserved

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<p>Distinct Proteins in Protein Corona of Nanoparticles Represent a Promising Venue for Endogenous Targeting – Part II: In vitro and in vivo Kinetics Study</p>

Cited by 16 publications

References 95 publications

Silver Nanostructures: Limited Sensitivity of Detection, Toxicity and Anti-Inflammation Effects

Silver Nanostructures: Limited Sensitivity of Detection, Toxicity and Anti-Inflammation Effects

Nanosilver in Biomedicine: Advantages and Restrictions

Nano‐Mediated PDT as a Multifunctional Immunomodulatory Agent in the Intricate Milieu of Melanoma

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