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

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

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

New Nanomedicine Approaches Using Gold-thioguanine Nanoconjugates as Metallo-Ligands

Gold-thioguanine nanoconjugates (AuNP-TG) of size 3-4 nm were synthesized and the ratio between gold and 6-thioguanine (TG) was estimated as ~1:1.5 using a cyanide digestion method and confirmed by flame atomic absorption spectroscopic analysis. AuNP-TG constructs showed high in vitro stability under different pH conditions and biologically relevant solutions for a period of 24 h. Reaction of AuNP-TG with europium or platinum salts resulted in the formation of organized self-assembled metallo-networks

Gold Nanoparticle Based Immunostrip Assay Method for Detection of Protein-A

We have successfully developed gold nanoparticle based immunostrip assay to detect protein-A (PA). Rabbit polyclonal antibody IGg (αPA) that has affinity to PA was conjugated to gold nanoparticles (GNPs) and the gold nanoconjugate (αPA-GNP) was used to detect protein-A by simple immunostrip assay method. ELISA experiments were used to confirm the retention of binding affinity of antibody towards protein-A after conjugation with gold nanoparticles