A Novel Method to Monitor Sequential Displacement of Capped Ligands in Gold Nanoparticles [abstract]

Nanoscience Poster SessionNanochemistry of ligand displacement reactions has attracted much attention in recent years for the development of myriad of new gold nanomaterials. Gold nanoparticles have shown applications ranging from tumor imaging agent in nanomedicine to single electron devices in information technology. New gold materials are synthesized by exchange of neutral or anionic ligands with thiolated molecules. Completion of ligand substitution reactions in gold nanoparticles are monitored by using UV-Vis spectrometry. However, there are no methods available to monitor the sequence of the ligand substitution reactions. Monitoring and predicting the sequence of ligand substitutions would provide a convenient handle for the design and development of hybrid nanomaterials containing two or more ligands. In this context, we have developed a novel technique utilizing disc centrifuge systems to monitor the sequential displacement of ligands in various gold nanoconstructs. In our studies, we have used gold nanoparticles stabilized with both anionic and neutral ligands. Gold nanoparticles of various different substitutions have been identified and characterized by disc centrifuge systems. Details of substitution reactions and mechanism on monitoring the sequential displacement using strong ligands will be presented

A Comparative Study between Antibody and Peptide Conjugated Gold Nanoparticles for In Vivo Targeting of EGFR in Pancreatic Cancer Bearing Mice Models [abstract]

Nanoscience Poster SessionPancreatic cancer is the fourth leading cause of cancer related deaths in the United States due to its severe aggressiveness and lethal malignancy. Epidermal Growth Factor Receptor (EGFR) is over expressed in more than 95% of human pancreatic cancer patients. A number of peptides and monoclonal antibodies have been developed to target the EGFR in pancreatic cancer. Our research has focused on developing EGFR targeting biomolecule conjugated gold nanoparticles for the diagnosis and staging of various cancers. In this study, we synthesized a series of Antibody EGFR and EGFR-peptide conjugated AuNPs. We investigated the in vivo EGFR targeting characteristics of these conjugates in pancreatic tumor bearing SCID mice models. Our investigation establishes that the peptide conjugated AuNPs have high in vivo mobility and targets pancreatic tumor effectively. We have also established that EGFR-peptide -AuNP conjugates act as better X-ray contrast agents for early detection of pancreatic cancer in mice models. The details of this comparative study will be presented in this poster

Synthesis, structure, spectral and electron-transfer properties of octahedral-[Co<SUP>III</SUP>(L)<SUB>2</SUB>]<SUP>+</SUP>/[Zn<SUP>II</SUP>(L)<SUB>2</SUB>] and square planar-[Cu<SUP>II</SUP>(L){OC(=O)CH<SUB>3</SUB>}] complexes incorporating anionic form of tridentate bis(8-quinolinyl)amine [N<SUP>1</SUP>C<SUB>9</SUB>H<SUB>6</SUB>-N<SUP>2</SUP>-C<SUB>9</SUB>H<SUB>6</SUB>N<SUP>3</SUP>, L<SUP>-</SUP>] ligand

The reaction of bis(8-quinolinyl)amine [N1C9H6-N2H-C9H6N3, LH] with CoII(ClO4)2 . 6H2O in methanol under aerobic conditions results in a new class of [CoIIIN6]+ (1+) chromophore incorporating an sp2-amido nitrogen center (N2) in the ligand frame. During the course of the reaction, the cobalt ion has been oxidized from its starting +2 oxidation state to +3 state in 1. The reaction of LH with the Cu-acetate yields monomeric square planar complex, [CuII(L){OC(=O)CH3}] (2). The same copper complex 2 is also obtained from Cu(ClO4) . 6H2O in presence of CH3COONa as base. On the other hand, the reaction of Zn(ClO4) . 6H2O with LH results in octahedral complex ZnII(L)2 (3). The Cu(II) complex 2 displays a four-line EPR spectrum at room temperature. Crystal structure of the free ligand (LH) shows that the amine proton [N(2)H] is hydrogen-bonded with the terminal quinoline nitrogen centers [N(1) and N(3)]. The crystal structure of 1 confirms the meridional geometry of the complex cation. The square planar geometry of copper complex 2 is confirmed by its crystal structure where the acetate function behaves as a monodentate ligand. The free ligand, LH, is found to be highly acidic in acetonitrile-water (1:1) medium and correspondingly the amine proton (NH) readily dissociates leading to its L- form even in absence of any external base. The pKb value of L- is determined to be 2.6. Both cobalt and copper complexes do not show any expected spin-allowed d-d transitions, possibly have masked by the intense charge-transfer transitions. However, in case of cobalt complex 1, one very weak unusual spin-forbidden 1A1g &#8594; 3T1g transition has been observed at 935 nm. The quasi-reversible cobalt (III)&#8596; cobalt(II) reduction of 1 is observed at E0, -1.0 V versus SCE. The reactions of bis(8-quinolinyl)amine [N1C9H6-N2H-C9H6N3, LH] with CoII(ClO4)2 . 6H2O, ZnII(ClO4)2 . 6H2O and CuII-acetate result in octahedral-[CoIII(L-)2]+ and [ZnII(L-)2] and square planar-[CuII(L-){-OC(=O)CH3}] complexes, respectively, incorporating an sp2-amido nitrogen center (N2) in the coordinated ligand frame of L. The structural, spectral and electrochemical aspects of the complexes have been described

Relative study between anti-EGFR and GE-11 peptide conjugated gold nanoparticles for in vivo targeting in pancreatic cancer [abstract]

Pancreatic cancer is the fourth leading cause of cancer related deaths in the United States due to its severe aggressiveness and lethal malignancy. Epidermal Growth Factor Receptor (EGFR) is over expressed in more than 95% of human pancreatic cancer patients. A number of peptides and monoclonal antibodies have been developed to target the EGFR in pancreatic cancer. Our research has focused on developing EGFR targeting biomolecule conjugated gold nanoparticles for the diagnosis and staging of various cancers. In this study, we have synthesized a series of Antibody EGFR and EGFR-peptide (GE-11) conjugated AuNPs. We investigated the in vivo EGFR targeting characteristics of these conjugates in pancreatic tumor bearing SCID mice models. Our investigation has provided evidence that the peptide conjugated AuNPs have high in vivo mobility and targets pancreatic tumor effectively. We have also established that the EGFR-peptide-AuNP conjugates serve as better X-ray contrast agents for early detection of pancreatic cancer in mice models. The details of this comparative study will be presented in this poster

Green nanotechnology from cumin phytochemicals : generation of biocompatible gold nanoparticles

Published in final edited form as: Int J Green Nanotechnol Biomed. 2009 January 1; 1(1): B39-B52. doi:10.1080/19430850902931599.The powerful antioxidant characteristics of various phytochernicals within cumin prompted us to test their efficacy in reducing sodium tetrachloroaurate to corresponding gold nanoparticles. We, herein, report an unprecedented synthetic route that involves the production of well-defined spherical gold nanoparticles by simple mixing of cumin to an aqueous solution of sodium tetrachloro aurate. Production of gold nanoparticles in this cumin-mediated Green Nanotechnological process is achieved under biologically benign conditions. The gold nanoparticles generated through cumin-mediated process did not aggregate suggesting that the cocktail of phytochemicals including proteins serve as excellent coatings on nanoparticles and thus, provide robust shielding from aggregations. In addition, the phytochemical coatings on nanoparticles have rendered nontoxic features to these 'Green Gold Nanoparticles' as demonstrated through detailed MTT assays performed on 'normal fibroblast cells. Results of our studies presenting a new 'Nano-Naturo' connection for the production and utility of gold nanoparticles for potential applications in nanomedicine and nanotechnology are discussed in this paper.This work has been supported by the generous support from the National Institutes of Health/National Cancer Institute under the Cancer Nanotechnology Platform program (grant number: 5R01CA119412-01), NIH - 1R21CA128460-01 and University of Missouri-Research Board - Program C8761 RB 06-030

Photoacoustic Detection of Circulating Prostate, Breast and Pancreatic Cancer cells using targeted Gold Nanoparticles: Implications of Green Nanotechnology in Molecular Imaging

Nanoscience Poster SessionCirculating tumor cells are hallmarks of metastasis cancer. The presence of circulating tumor cells in blood stream correlates with the severity of disease. Photoacoustic imaging (PA) of tumor cells is an attractive technique for potential applications in diagnostic imaging of circulating tumor cells. However, the sensitivity of photoacoustic imaging of tumor cells depends on their photon absorption characteristics. In this context, gold nanoparticle embedded tumor cells offer significant advantages for diagnostic PA of single cells. As the PA absorptivity is directly proportional to the number of nanoparticles embedded within tumor cells, the propensity of nanoparticles to internalize within tumor cells will dictate the sensitivity for single cell detection. We are developing biocompatible gold nanoparticles to use them as probes as part of our ongoing effort toward the application of X ray CT Imaging, Ultra Sound (US) and photoacoustic imaging of circulating breast, pancreatic and prostate tumor cells. We, herein report our latest results which have shown that epigallocatechin gallate (EGCG)-conjugated gold nanoparticles (EGCG-AuNPs) internalize selectively within cancer cells providing threshold concentrations required for photo acoustic signals. In this presentation, we will describe, our recent results on the synthesis and characterization of EGCG gold nanoparticles, their cellular internalization and photo acoustic imaging of PC-3 prostate cancer cells and PANC-1 pancreatic cancer cells

An Effective Strategy for the Synthesis of Biocompatible Gold Nanoparticles Using Cinnamon Phytochemicals for Phantom CT Imaging and Photoacoustic Detection of Cancerous Cells

This is a post-print version of the Pharmaceutical Research Article. The original publication is available at www.springerlink.com. DOI 10.1007/s11095-010-0276-6Purpose: The purpose of the present study was to explore the utilization of cinnamon coated gold nanoparticles (Cin-AuNPs) as CT/optical contrast enhancement agent for detection of cancer cells. Methods: Cin-AuNPs were synthesized by a “Green” procedure and the detailed characterization has been performed by physic-chemical analysis. Cytotoxicity and cellualar uptake studies were carried out in normal human fibroblast and cancerous (PC-3 and MCF-7) cells respectively. The efficacy of detecting cancerous cells was monitored using photoacoustic technique. In vivo biodistribution was studied after IV injection of Cin-AuNPs in mice and a CT phantom model was generated. Results: Biocompatible Cin-AuNPs were synthesized with high purity. Significant uptake of these gold nanoparticles was observed in PC-3 and MCF-7 cells. Cin-AuNPs internalized in cancerous cells facilitate detectable photoacoustic signals. In vivo biodistribution in normal mouse shows steady accumulation of gold nanoparticles in lungs and rapid clearance from blood. Quantitative analysis of CT values in phantom model reveals that the cinnamon phytochemicals coated AuNPs has reasonable attenuation efficiency. Conclusions: The results indicate that these non-toxic Cin-AuNPs can serve as excellent CT/ photoacoustic contrast enhancement agents and may provide a novel approach toward the tumor detection through nanopharmaceuticals.This work has been supported by grants from the National Institutes of Health/National Cancer Institute under the Cancer Nanotechnology Platform program (grant number: 5R01CA119412-01), NIH - 1R21CA128460-01; NIH-SBIR-Contract no. 241, and University of Missouri-Research Board - Program C8761 RB 06-030

Comparative oncology and clinical translation of glyco protein conjugated gold nano therapeutic agent (GA-198AuNP) [abstract]

Nanoscience Poster SessionAs part of our efforts toward clinical translation of GA-198AuNP, our studies are focused on therapeutic efficacy of nanoparticulate GA198AuNP agent in dogs with prostatic carcinoma. The overall goal is to gain clinical insights on therapeutic efficacy of GA198AuNP in a large animal model. We have performed a phase I clinical trial using GA-AuNP administered intravenously or intratumorally by injection or infusion. CT scans were performed prior to injection and 24 hours post injection in 3 of the 4 dogs. Following injections, dogs were allowed further treatment as recommended by the primary attending clinician. Four dogs have been treated to date. Complications related to GA-AuNP treatment were not observed, and all 4 dogs received adjunctive treatment with radiation therapy and/ or chemotherapy. These preliminary studies have clearly provided compelling evidence on the therapeutic potential of biocompatible GA-AuNP for their utility as novel therapeutic agents in treating various types of inoperable solid tumors. Intra-tumoral and intravenous administration of GA-AuNP is safe in dogs with spontaneously occurring tumors. As further therapeutic efficacy studies continue, the outcome of this clinical trial in a large animal model will generate therapeutic efficacy data which will be used for filing IND application for Phase I clinical trial studies. This clinical translation effort provides significant advances in terms of delivering optimum therapeutic payloads into prostate cancers with subsequent reduction in tumor volume, thus may effectively reduce/eliminate the need for surgical resection. This presentation will include details of clinical translation of GA198AuNP in prostate tumor bearing dogs

Smart gold nanosensor for easy sensing of lead and copper ions in solution and using paper strips

A smart gold nanosensor, Au–TA–DNS is designed that can rapidly detect very low concentrations of Pb2+ and Cu2+ ions. The nanosensor develops a visible blue colour in solution and on paper strips, because of the formation of nanoparticle aggregates upon binding with metal ions. Due to the presence of dansyl fluorophore, Au–TA–DNS also exhibits significant fluorescence quenching following Pb2+ and Cu2+ binding in aqueous medium, which is proportional to the concentration of ions. Both colorimetric and fluorometric analyses are very much selective for lead and copper ions with a detection limit of ≤10.0 ppb. The paper based sensing method has the advantage of cost-effectiveness and would be useful for wide range of field-test applications such as water quality monitoring process

A paper based microfluidic device for the detection of arsenic using a gold nanosensor†

A paper based microfluidic device is fabricated that can rapidly detect very lowconcentrations of As3+ ions using a gold nanosensor, Au–TA– TG. This simple but efficient system develops a visible bluish-black colour precipitate due to the formation of nanoparticle aggregates through transverse diffusive mixing of Au–TA–TG with As3+ ions on a paper substrate. The approach is extremely selective for arsenic with a detection limit of 1.0 ppb, which is lower than the WHO's reference standard for drinking water