Gemcitabine (Gemzar(R)) is an effective chemotherapeutic drug approved for treatment of several cancers, including non-small cell lung cancer (NSCLC), pancreatic, breast and ovarian cancer. However, its use has been limited due to its short half-life and significant systemic toxicity. This proposal utilizes a novel Lipid-Calcium-Phosphate (LCP) nanoparticle platform for the design of multifunctional targeted nanoparticles (NP) to deliver gemcitabine triphosphate (GTP) and 111Indium to cancer cells. In these novel particles GTP is a therapeutic agent and 111Indium is a radio-imaging agent. These resulting LCP-GTP-Indium theranostic nanoparticles will be evaluated for efficacy in lung tumor models and imaging capabilities. The novel NPs will also be evaluated for preliminary toxicity in normal mice. The targeted LCP-GTP-Indium theranostic nanoparticles are expected to increase the half-fife and lower the toxicity of gemcitabine while simultaneously allowing for tumor imaging capabilities. Development of GTP+lndium nanoparticles will improve the delivery of a known chemotherapy drug and enhance the potential for expanded use of this drug in lung and other cancers. Furthermore 111Indium will allow in vivo tracking and imaging of NP without affecting the NP characteristics or biodistribution. This diagnostic capability will enable individualized treatment based on biodistribution, leading to a true personalized medicine product.
NIH Spending Category: Bioengineering; Cancer; Lung; Lung Cancer; Nanotechnology; Orphan Drug; Pancreatic Cancer; Rare Diseases
Project Terms: Affect; base; Biodistribution; calcium phosphate; cancer cell; Characteristics; chemotherapy; design; Development; Diagnostic; Drug Kinetics; Drug usage; gemcitabine; gemzar; Half-Life; Image; improved; in vivo; Indium; Lipids; Lung; Lung Neoplasms; malignant breast neoplasm; Malignant neoplasm of ovary; Malignant neoplasm of pancreas; Malignant Neoplasms; Medicine; Modeling; Mus; nanoparticle; Non-Small-Cell Lung Carcinoma; novel; Nude Mice; particle; Pharmaceutical Preparations; Radio; research and development; subcutaneous; theranostics; Therapeutic Agents; Tomography, Emission-Computed, Single-Photon; Toxic effect; Treatment Efficacy; tripolyphosphate; tumor
