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The Penn State Research Foundation

Gail L Matters

Jill P Smith

Mark Kester

John F Harms

James H Adair

Neil D Christensen

Erhan I Altinoglu

Thomas T Morgan

Brian M Barth

Sriram S Shanmugavelandy

James M Kaiser

Christopher McGovern

Rahul Sharma

Non-aggregating resorbable calcium phosphosilicate nanoparticles (CPNPs) are bioconjugated to targeting molecules that are specific for particular cells. The CPNPs are stable particles at normal physiological pH. Chemotherapy and imaging agents may be integrally formed with the CPNPs so that they are compartmentalized within the CPNPs. In this manner, the agents are protected from interaction with the environment at normal physiological pH. However, once the CPNPs have been taken up, at intracellular pH, the CPNPs dissolve releasing the agent. Thus, chemotherapeutic or imaging agents are delivered to specific cells and permit the treatment and/or imaging of those cells. Use of the bioconjugated CPNPs both limits the amount of systemic exposure to the agent and delivers a higher concentration of the agent to the cell. The methods and principals of bioconjugating CPNPs are taught by examples of bioconjugation of targeting molecules for breast cancer, pancreatic cancer, and leukemia.

Bioconjugation of calcium phosphosilicate nanoparticles for selective targeting of cells in vivo

Gastrin mRNA down-regulation using either stable transfection of an antisense gastrin cDNA or one of three shRNA (short hairpin RNA) constructs achieves significant reduction in growth of human pancreatic cancer. Tumor growth rate and incidence of metastases in both wild type and transfected pancreatic cancer cells is directly proportional to the degrees of gastrin mRNA expression. In order to avoid rapid degradation of injected siRNA, nanoliposomes can be loaded with gastrin siRNA and used to deliver the siRNA to the tumors. Significant reduction of tumors in mice using siRNA loaded nanoliposomes is achieved. Uptake of pegylated nanoliposomes by tumor cells depends upon the pegylation percentage.

Composition and method for the treatment of gastrin mediated cancers

Human pancreatic cancer cells possess a distinct plasma membrane CCK receptor variant that can be differentiated from the classic CCK-B receptor with selective monoclonal antibodies. Use of this receptor may be helpful in early detection or treatment of patients with pancreatic cancer.

Identification and characterization of a specific CCK-C receptor antibody for human pancreatic cancer and its use for early detection and staging of pancreatic cancer

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Hummelstown, PA, United States of America

Gail L Matters