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PROJECT 2: NANO SCALE DRUG DELIVERY SYSTEM

MicroRNAs (miRNAs)-based therapy is one of the most promising new therapeutic paradigms in medicine that focuses on manipulating and inducing cellular re-equilibrium of deregulated miRNA expression profiles by the inhibition or overexpression of miRNA. Although miRNA has shown much promise for the treatment of a broad spectrum of diseases, including cancer, the delivery of miRNA is a challenge due to the vulnerability of miRNA to serum nucleases, the proneness to cause off- target effects, and the requirement for delivery into the cytosol of target cells. Thus, novel, non-viral, delivery systems are needed to effectively deliver miRNA to the target tissue. The objective of this project is to develop a clinical, translatable, approach for the delivery of miRNA that capitalizes on the unique features possessed by non-viral lipid nanoparticles (LNPs) encapsulated with miRNA. These features include enhanced delivery to the cytosol of the tumor cells and cell membrane permeability to macromolecules, which is believed to facilitate miRNA internalization. Also the LNP platform provides the ability to target specific tissue, control the spatial distribution as well as temporal release profile of miRNA, and combined delivery of established drugs and therapeutic miRNAs.

TEM Images of the Liposome Nanoparticles

Confocal Images of Cell Uptake of LNPs

PUBLICATIONS


  1. 1“Drug-Loaded Particles: "Trojan Horses" in the Therapy of Atherosclerosis”, Nikolaos Tsigkas, Srivatsan Kidambi,  Ahmed Tawakol, Yiannis S. Chatzizisis, Atherosclerosis, 2016, doi: 10.1016/j.atherosclerosis.2016.06.050


  1. 2“Hyaluronic Acid-Conjugated Liposome Nanoparticles for Targeted Delivery to CD44 Overexpressing Glioblastoma Cells” Stephen Hayward, Christina Wilson, Srivatsan Kidambi*, Oncotarget, 2016, doi: 10.18632/oncotarget.8926


  1. 3“Targeted Delivery of MicroRNA-125a-5p by Engineered Lipid Nanoparticles for the Treatment of HER2 positive Metastatic Breast Cancer”, Stephen Hayward, David Francis, Parviz Kholmatov, Srivatsan Kidambi*, Journal of Biomedical Nanotechnology, 12(3), 554-68, 2016 doi: 10.1166/jbn.2016.2194 

  2. 4““Ionic Driven Embedment of Hyaluronic Acid Coated Liposomes in Polyelectrolyte Multilayer Films for Local Therapeutic Delivery”, Stephen Hayward, David Francis, Matthew Sis, Srivatsan Kidambi*,  Nature Scientific Reports, 5, 14683, 2015, doi: 10.1038/srep14683

  3. 5“Dye-doped silica encapsulated magnetic nano-assemblies for dual optical/MRI imaging and hyperthermia", Sunil Kumar, Dhirendra Bahadur, Amita Daverey, Vahid Khalilzad-Sharghi, Niroj Sahu, Srivatsan Kidambi, Shadi Othman,  RSC Advances, 5, 53180-53188, 2015 doi: 10.1039/C5RA07632C