Clinical translation of a novel cancer nanothereapeutic agent : bench to bedside from a small company perspective [abstract]

Nanoparticles of gold are inherently multifunctional in their diagnostic and therapeutic capabilities. 198Au, provides a desirable beta energy emission and half-life for effective destruction of tumor cells/ tissue(?max = 0.96 MeV; half -life of 2.7 days). The range of the 198Au [beta]-particle is sufficiently long to provide cross-fire effects of radiation dose delivered to cells within the prostate gland and short enough to minimize significant radiation dose to critical tissues near the periphery of the capsule. In order to capitalize on the well known tumor affinity of gold nanoparticles to tumor vasculature, Nanoparticle Biochem Inc (NBI), has developed proprietary technology that allows efficient conversion of radioactive gold-198 to its corresponding therapeutic nanoparticles with subsequent stabilization via conjugation with Gum Arabic protein matrix. As part of the SBIR Phase I effort, Nanoparticle Bicohem Inc (NBI) has successfully completed detailed therapeutic efficacy studies in prostate tumor bearing mice and toxicity studies of the non radioactive surrogate of NBI 29 in pigs. Intratumoral injection of NBI's proprietary gold nanoparticle based injectable agent: 198AuNP-GA (NBI-29), has unequivocally demonstrated that over 90% of the injected dose remains in the tumor over a 24 hour (and longer) time period and that the agent effectively shrinks and suppresses the growth of prostate tumors in mice to such levels that are not commonly observed with any chemo or radiotherapeutic agent (Katti, Kannan and others in Nanomedicine Volume 6, Issue 2, Pages 201-209 April 2010; featured article on the cover page in April 2010 issue). No toxic side effects were noted for over 40 days of studies in mice and for over 120 days investigation in pigs (using the non radioactive surrogate). Limited Phase I clinical trial studies in client owned dogs with naturally occurring prostate tumors, which mimic androgen independent prostate tumors in men, have already provided unequivocal evidence on the realistic clinical potential of NBI 29 as a new generation nanotherapeutic agent for treating inoperable solid tumors. In order to clinically translate the therapeutic potential of NBI 29 for treating prostate tumor human patients, Nanoparticle Biochem Inc has recently entered into a joint product development effort with Shasun Pharmaceutical Company of India. Shasun-NBI LLC will focus product development efforts aimed at completion of toxicity/therapeutic efficacy in dogs to allow filing of an IND application with the US FDA to commence Phase I clinical trials in human prostate cancer patients. Product development efforts, incorporating platform nanotechnology of Shasun-NBI LLC, as outlined above, will be carried out in collaboration with internationally reputed group of interdisciplinary scientists, consultants and cancer therapy experts within the University of Missouri and chosen from other locations with expertise in (i) therapeutic isotope production; (ii) nanotechnology as it relates to applications in nanomedicine; (ii) tumor biology (iii) radiation/clinical and surgical oncology; (iii) medical physics and dosimetry; (iv) veterinarians with strong comparative oncology track record; and (v) conducting Phase I-III clinical trials leading to final approval by the US FDA Implications for prospective investors in terms of the pontifical of Shasun-NBI LLC's 'Platform Nanotechnology' for the development of sophisticated therapy agents for treating hepatocellular and pancreatic cancers will be presented

Nanomedicine approach for sustained release delivery of Avastin : treatment for PXE and AMD [abstract]

Gold nanoparticles possess unique properties including preferential binding to leaky blood vessels, ability to bind to a variety of ligands, with no evidence of cellular toxicity, making them an excellent platform for targeted sustained release of drugs. Avastin (Bevacizumab) is a humanized monoclonal antibody specifically targeting vascular endothelial growth factor (VEGF) that has found widespread use in inhibiting intraocular neovascularization manifested in macular degeneration and proliferative diabetic retinopathy. The conjugation of gold nanoparticles (AuNP) with Avastin (Av) yields AvAuNP nanoconjugates. Avastin conjugated gold nanoparticles (AvAuNP) can be used as therapeutic agents in the treatment of ophthalmic neovascular disorders, such as macular degeneration, PXE and proliferative diabetic retinopathy. AvAuNP nanoconjugate is a potential clinical therapeutic agent and has demonstrated excellent ability to deliver Avastin for sustained release of therapeutic dose within the eye. The design and development of AvAuNP conjugate would help in the initiation and completion of preclinical evaluations aimed at determining the ability to achieve long-term suppression of intraocular neovascularization in large animals. INVENTOR(S): Ravi Shukla; Kavita K. Katti; Raghuraman Kannan; Dean Hainsworth and Kattesh V. Katti CONTACT INFO: Paul Hippenmeyer, Ph.D., M.B.A.; [email protected]; (573)-882-047

Indigenous ecological knowledge as social capital: How citizen science can help us replenish the bank

*Background/Question/Methods* 

In our increasingly urban world, indigenous knowledge of local ecology is declining rapidly, because survival in industrialized urban environments does not depend on knowing the details of local flora, fauna, or phenologies. While traditional ecological knowledge has been documented since 1980s, this is has been largely descriptive, e.g., ethnobotany of sacred groves, cultivation practices, or use of medicinal plants. Until recently, conservation biologists and managers of protected areas have followed western models of conservation that exclude local people and often abandon local ecological knowledge. However, many scientific studies of local ecosystems would not have been possible without the knowledge-base of indigenous people helping researchers. Yet, careful scientific analysis of such knowledge systems is scarce, except in some commercial applications such as forestry or fisheries. Further, even in rare instances when park managers have recruited knowledgeable locals as partners in PA management, the bureaucracy ended up dissipating ecological knowledge rather than sustaining it. The challenge therefore is to understand the epistemology of ecological knowledge, especially the costs and benefits to local people, to help create novel management regimes which provide new incentives for sustaining such knowledge even as traditional dependencies on natural resources are transformed for long-term sustainability of biodiversity. 

*Results/Conclusions*

This paper reviews the literature on indigenous ecological knowledge in South Asia, to establish a baseline for systematic epistemological analyses. Examples include the Bihari bird-trappers assisting the Bombay Natural History Society's bird-ringing projects, Irulas helping snake research at Madras Crocodile Bank, Kanis supporting a variety of research projects, including our own, in Kalakad-Mundanthurai Tiger Reserve over the past two decades, and the modern day settlers in Andaman Islands who have turned from over-harvesting and poaching to sustainable cultivation of Edible-nest Swiftlets. We argue that indigenous knowledge is useful not only for monitoring ecosystems or determining use of natural resources, but more importantly for generating fundamental scientific insights, and adding to the knowledge part of our collective social capital. Even as indigenous knowledge is being lost, volunteer-based Citizen Science projects are recruiting amateur naturalists, especially in urban areas, to monitor and study local biodiversity. Such approaches need to be extended into genuinely participatory research programs where indigenous people are engaged in generating and sustaining ecological knowledge, from traditional and modern scientific perspectives, to become well-informed stewards of the socio-ecological systems we inhabit from local to global scales. This is a crucial step towards slowing the loss of biodiversity by reversing our collective loss of knowledge of biodiversity

Green nantocehnology in dual medical and national defense applications : global perspectives on formal training and education

This presentation was part of the Sensing: Biomarkers, Biometrics, and CBRNE Platforms Panel in which experts addressed the challenge of sensing, and sense-making in support of the national security analytic process. Perspectives emphasized the technology strengths, limitations, and operational relevance

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

Stability of Hill Slopes and Foundation Condition at Radio Astronomy Centre Ootacamand

Stability aspects of hill slopes and foundation considerations of Radio Astronomy Centre at Ootacamand are described. The analysis of slopes indicated that if joints are not covered, the material in joints may lose strength and the slopes may enter a state of instability. Footings with inclined legs were found to resist the horizontal forces, pull and overturning movements. Lime piles adopted for strengthening soft material at one of the tower locations were found to be effective

A comparative clinical study on efficacy of Mashaparni and Kapikachu in Oligospermia

Introduction: Oligospermia is deficiency of sperm cells in semen. It is one of the main causes for male infertility. Prevalence of male infertility is around 7%. Recent studies showed that nearly 2-5% couple around world is suffering from the problems of inability to achieve conception. The normal process of spermatogenesis will be affected due to mechanical life, stress, strain and unhealthy food and various changes occur in the life style. Objective: To evaluate the efficacy of Mashaparni and Kapikachu in Oligospermia. Materials and Methods: Data was collected by randomized sampling through lottery method with a minimum of 30 subjects of Oligospermia with respect to age and sex, irrespective of caste, religion and socio economic status. These subjects were assigned into 2 groups A and B with 15 subjects in each group. Duration of the intervention was 3 months. Results: Results obtained were statistically insignificant between both the groups. Conclusion: On the basis of the result of this study it was concluded that, both prescribed drugs will increase sperm count significantly

EFFECTIVENESS OF PLANNED TEACHING PROGRAMME ON KNOWLEDGE REGARDING CERVICAL CANCER AMONG WOMENâ€.

Objectives: To determine the effectiveness of planned teaching programme (PTP) on knowledge regarding cervical cancer among women at selected urban area Karad and to find out the association between knowledge scores with selected sociodemographic variables among women in selected urban areas at Karad.Methods: Evaluative research approach was used for the study and conducted in urban area Koyana Vasahat, Karad, Maharashtra, India, using one group pre- and post-test design. Systematic proportionate sampling technique was used for selecting 60 women. On the 1st day, structured knowledge questionnaire was used for collecting data, and PTP on knowledge regarding cervical cancer was conducted, followed by posttest on the 7th  day. The data collected, tabulated, and analyzed in terms of objectives of the study using descriptive and inferential statistics.Results: The mean pretest value was 7 and the mean posttest value was 11 with a difference of 4. The paired t-value was 10.2, (p<0.05) showing a significant increase in the knowledge regarding cervical cancer and its prevention. There was no significant association between knowledge scores of women with the selected demographic variables.Conclusion: The study showed that the PTP on cervical cancer was effective in improving the knowledge of women and thus helps them to understand the harmful effects of cervical cancer as well as to take necessary steps for early detection and prevention.Keywords: Effectiveness, Planned teaching programme, Cervical cancer, Knowledge, Women

Agarose-stabilized gold nanoparticles for surface-enhanced Raman spectroscopic detection of DNA nucleosides

doi:10.1063/1.2192573 http://scitation.aip.org/getpdf/servlet/GetPDFServlet?filetype=pdf&id=APPLAB000088000015153114000001&idtype=cvips&prog=normal&doi=10.1063/1.2192573We present surface-enhanced Raman scattering (SERS) studies of DNA nucleosides using biologically benign agarose-stabilized gold nanoparticles (AAuNP). We compare the SERS activity of nucleosides with AAuNP to that of commercially obtained citrate-stabilized gold nanoparticles and find the SERS activity to be an order of magnitude higher with AAuNP. The higher SERS activity is explained in terms of the agarose matrix, which provides pathways for the gold nanoparticles to have distinct arrangements that result in stronger internal plasmon resonances.This work was supported through the University of Missouri Research Board grants URB04-023 (S.G.) and URB03-080 (M.C. and K.V.K.), NSF under Grant No. DMR-0413601and the NCI under Grant No. IR0ICA119412-01. The gold nanoparticles were produced and supplied by the University of Missouri Nanoparticle Production Core Facility

Green nanotechnology of MGF‑AuNPs for immunomodulatory intervention in prostate cancer therapy

Abstract Men with castration-resistant prostate cancer (CRPC) face poor prognosis and increased risk of treatment-incurred adverse effects resulting in one of the highest mortalities among patient population globally. Immune cells act as double-edged sword depending on the tumor microenvironment, which leads to increased infiltration of pro-tumor (M2) macrophages. Development of new immunomodulatory therapeutic agents capable of targeting the tumor microenvironment, and hence orchestrating the transformation of pro-tumor M2 macrophages to anti-tumor M1, would substantially improve treatment outcomes of CRPC patients. We report, herein, Mangiferin functionalized gold nanoparticulate agent (MGF-AuNPs) and its immunomodulatory characteristics in treating prostate cancer. We provide evidence of immunomodulatory intervention of MGF-AuNPs in prostate cancers through observations of enhanced levels of anti-tumor cytokines (IL-12 and TNF-α) with concomitant reductions in the levels of pro-tumor cytokines (IL-10 and IL-6). In the MGF-AuNPs treated groups, IL-12 was elevated to ten-fold while TNF-α was elevated to about 50-fold, while IL-10 and IL-6 were reduced by two-fold. Ability of MGF-AuNPs to target splenic macrophages is invoked via targeting of NF-kB signaling pathway. Finally, therapeutic efficacy of MGF-AuNPs, in treating prostate cancer in vivo in tumor bearing mice, is described taking into consideration various immunomodulatory interventions triggered by this green nanotechnology-based nanomedicine agent