Research Interests: Chemistry, Organic Chemistry, Computational Biology, Proteomics, Metal Nanoparticles, and 11 moreHumans, Gold, Female, Bioconjugate Chemistry, Particle Size, Surface Properties, Cell Proliferation, Structure activity Relationship, Antineoplastic Agents, Biochemistry and cell biology, and Ovarian Neoplasms
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Research Interests: Materials Science, Technology, Nanoparticle, Metal Nanoparticles, Biological Sciences, and 15 moreHumans, Gold nanoparticle, Gold, Gold Nanoparticles, Fibroblast Growth Factor, CHEMICAL SCIENCES, Particle Size, Surface Properties, Surface Charge, Protein Conformation, Growth Factor, Intracellular Signaling, Vascular Endothelial Growth Factor, Angiogenesis inhibitors, and Basic Fibroblast Growth Factor
Gold nanoparticles (AuNPs) have been widely studied for use in disease therapeutics as targeting and imaging agents, drug delivery vehicles and as self-therapeutics. When AuNPs interact with the biological milieu they form a corona layer,... more
Gold nanoparticles (AuNPs) have been widely studied for use in disease therapeutics as targeting and imaging agents, drug delivery vehicles and as self-therapeutics. When AuNPs interact with the biological milieu they form a corona layer, which is predominantly composed of proteins. The outer “soft” layer is dynamic and here proteins are free to exchange over time. The inner “hard” layer on the other hand consists of proteins firmly bound to the NP surface. The Vromans effect predicts that given a limited surface area, low affinity, high abundance proteins, that first attach to the surface, are over time replaced by high affinity, low abundance proteins. Our aim was to enrich low abundance proteins on the AuNP surface to probe for differentially expressed proteins that are not detected by traditional methods of protein identification. We studied the binding of ovarian cell lysates (cancerous and non cancerous) to 10 nm sized positively and negatively charged AuNPs. The formation of ...
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Numerous cellular processes rely on biomolecular interactions such as proteinprotein in-teractions, proteinnucleic acid interactions, enzyme activity, and cell surface recognition. These interactions are primarily due to complementary... more
Numerous cellular processes rely on biomolecular interactions such as proteinprotein in-teractions, proteinnucleic acid interactions, enzyme activity, and cell surface recognition. These interactions are primarily due to complementary electrostatic, hydrophobic, and po-lar ...
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Research Interests: Chemistry, Kinetics, Nanoparticle, Nanoparticles, Magnetic Resonance Spectroscopy, and 13 moreMedicine, Gold nanoparticle, Gold, Temperature, CHEMICAL SCIENCES, Time Factors, Surface Properties, Sensitivity and Specificity, Monolayer, Ligands, Boron Compounds, Chemical Engineering Communications, and Colloidal Gold
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ABSTRACT A gold nanoparticle functionalized with substrates for alpha-chymotrypsin was fabricated to afford an enzyme modulator that exhibited enzyme-specific activation coupled with general inhibition of other proteases.
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Recently we reported that gold nanoparticles (AuNPs) inhibit ovarian tumor growth and metastasis in mice by reversing epithelial-mesenchymal transition (EMT). Since EMT is known to confer drug resistance to cancer cells, we wanted to... more
Recently we reported that gold nanoparticles (AuNPs) inhibit ovarian tumor growth and metastasis in mice by reversing epithelial-mesenchymal transition (EMT). Since EMT is known to confer drug resistance to cancer cells, we wanted to investigate whether anti-EMT property of AuNP could be utilized to sensitize ovarian cancer cells to cisplatin. Herein, we report that AuNPs prevent cisplatin-induced acquired chemoresistance and stemness in ovarian cancer cells and sensitize them to cisplatin. AuNPs inhibit cisplatin induced EMT, decrease the side population cells and key stem cell markers such as ALDH1, CD44, CD133, Sox2, MDR1 and ABCG2 in ovarian cancer cells. Mechanistically, AuNPs prevent cisplatin-induced activation of Akt and NF-kB signaling axis in ovarian cancer cells that are critical for EMT, stem cell maintenance and drug resistance. In vivo, AuNPs sensitize orthotopically implanted ovarian tumor to a low dose of cisplatin and significantly inhibit tumor growth via facilitat...
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Nanoparticles provide a potent tool for targeting and understanding disease mechanisms. In this regard, cancer cells are surprisingly resistant to the expected toxic effects of positively charged gold nanoparticles ((+)AuNPs). Our... more
Nanoparticles provide a potent tool for targeting and understanding disease mechanisms. In this regard, cancer cells are surprisingly resistant to the expected toxic effects of positively charged gold nanoparticles ((+)AuNPs). Our investigations led to the identification of MICU1, regulator of mitochondrial calcium uniporter, as a key molecule conferring cancer cells with resistance to (+)AuNPs. The increase in cytosolic [Ca(2+)]cyto in malignant cells induced by (+)AuNPs is counteracted by MICU1, preventing cell death. Pharmacological or siRNA-mediated inhibition of mitochondrial Ca(+2) entry leads to endoplasmic reticulum stress and sensitizes cancer cells to (+)AuNP-induced cytotoxicity. Silencing MICU1 decreases Bcl-2 expression and increases caspase-3 activity and cytosolic cytochrome c levels, thus initiating the mitochondrial pathway for apoptosis: effects further enhanced by (+)AuNPs. This study highlights the potential of nanomaterials as a tool to broaden our understanding...
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Inorganic nanoparticles provide promising tools for biomedical applications including detection, diagnosis and therapy. While surface properties such as charge are expected to play an important role in their in vivo behavior, very little... more
Inorganic nanoparticles provide promising tools for biomedical applications including detection, diagnosis and therapy. While surface properties such as charge are expected to play an important role in their in vivo behavior, very little is known how the surface chemistry of nanoparticles influences their pharmacokinetics, tumor uptake, and biodistribution. Using a family of structurally homologous nanoparticles we have investigated how pharmacological properties including tumor uptake and biodistribution are influenced by surface charge using neutral (TEGOH), zwitterionic (Tzwit), negative (TCOOH) and positive (TTMA) nanoparticles. Nanoparticles were injected into mice (normal and athymic) either in the tail vein or into the peritoneum. Neutral and zwitterionic nanoparticles demonstrated longer circulation time via both i.p. and i.v. administration, whereas negatively and positively charged nanoparticles possessed relatively short half-lives. These pharmacological characteristics w...
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We introduce a promising methodology to identify new therapeutic targets in cancer. Proteins bind to nanoparticles to form a protein corona. We modulate this corona by using surface-engineered nanoparticles, and identify protein... more
We introduce a promising methodology to identify new therapeutic targets in cancer. Proteins bind to nanoparticles to form a protein corona. We modulate this corona by using surface-engineered nanoparticles, and identify protein composition to provide insight into disease development. Using a family of structurally homologous nanoparticles we have investigated the changes in the protein corona around surface-functionalized gold nanoparticles (AuNPs) from normal and malignant ovarian cell lysates. Proteomics analysis using mass spectrometry identified hepatoma-derived growth factor (HDGF) that is found exclusively on positively charged AuNPs ((+)AuNPs) after incubation with the lysates. We confirmed expression of HDGF in various ovarian cancer cells and validated binding selectivity to (+)AuNPs by Western blot analysis. Silencing of HDGF by siRNA resulted s inhibition in proliferation of ovarian cancer cells. We investigated the modulation of protein corona around surface-functionali...