Development of nucleic acid delivery platform based on polymeric CXCR4 antagonists

DESCRIPTION provided by applicant Therapeutics based on nucleic acids NA promise to revolutionize treatment of multiple diseases but their widespread use is currently limited by the lack of efficient delivery methods We have recently developed a new NA delivery platform based on polymeric CXCR inhibitors PCX suitable as dual function systems for simultaneous NA delivery and inhibition of CXCR chemokine receptor The objective of this year Phase I project is to use the PCX platform to develop an innovative combination treatment of cholangiocarcinoma using PCX microRNA nanoparticles Clinical and experimental studies show that CXCR expression is associated with more aggressive disease higher primary tumor burden more metastases and shorter overall survival in cholangiocarcinoma The hypothesis of this project is that using PCX to deliver miR b inhibitor identified in our preliminary studies s potential target in cholangiocarcinoma will lead to improved overall anticancer activity We will accomplish the objectives through pursuing the following specific aims optimize PCX microRNA formulation parameters to obtain nanoparticles capable of simultaneous CXCR inhibition and microRNA delivery in cholangiocarcinoma and determine if delivery of miR b inhibitor by PCX improves overall survival in orthotopic rat model of cholangiocarcinoma The approach is innovative because of the dual function design of nanoparticles with CXCR inhibitory activity and microRNA delivery The proposed research is significant because it will establish widely applicable and versatile NA delivery platform that target chemokine networks as a way of improving therapeutic outcomes in cancer and other diseases with involvement of CXCR PUBLIC HEALTH RELEVANCE Nucleic acids represent a class of promising therapeutic agents in a broad range of diseases To take full advantage of these new therapeutics there is a critical need to develop reliable and efficient delivery methods The proposed research is relevant to public health because it will address the need for such methods by developing unique dual function nanoparticles to deliver microRNA as a way of treating a deadly form of liver cancer