Inhibition Of Intercellular Adhesion Molecule-1 In Lung Cancer Cells By Selective Sirna Nanoparticles

Lung cancer is the leading cause of malignancy related death in the United States of America. Although chemotherapy has been used for lung cancer, its safety and effectiveness are not satisfactory. The discovery of short interfering RNAs (siRNAs) provides a powerful tool to inhibit the interest such as ICAM-1(Intercellular Adhesion Molecule-1), which plays a crucial role in lung cell proliferation and tumor expansion, and offers an exciting target for treatment of lung cancers. The challenge with siRNA as therapeutic agents is its inherent instability in biological fluids and low distribution in cancer cells, so its targeted delivery to cancer tissues has frustrated scientists for decades.

During this one-year project, we propose to develop a new system by assembling three different RNAs as potential therapy for lung cancer: use a siRNA for inhibition of ICAM-1, incorporate it in a nanosize packing RNA of bacteriophage (pRNA), and make it a “smart-bomb‟ with an targeting RNA (tRNA) that specifically binds to a receptor found on lung cancer cells.

Therefore, the proposed siRNA-pRNA-tRNA nanoparticle consists of 1) therapeutic function of anti-ICAM-1 siRNA, 2) specific binding ability to a transferrin transport receptor of tRNA, and 3) pRNA of bacteriophage phi29 as a nanovector to carry both therapeutic siRNA and targeting RNA, respectively. We will evaluate therapeutic efficacy of this targeting strategy on lung cancer cells. If successful, this approach could be expected to treat lung cancers with improved selectivity and effectiveness compared to traditional chemotherapy. In addition, this work will help develop general principles that can be applied towards the establishment of RNA nanoparticles as a platform technology for delivering targeted therapeutic agents.

Husson University
Shuhua Bai, Ph.D.
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1 Year Pilot Grant

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