Nano-electroporation for high-specificity drug uptake using magneto-electric nanoparticles Grant

Nano-electroporation for high-specificity drug uptake using magneto-electric nanoparticles .

abstract

  • The human circulatory system can deliver a drug to every cell in the body; however, bringing a drug inside a tumor cell without affecting the healthy cells remains a formidable task. Availability of a technology capable of high-specificity delivery of anti-neoplastic drugs would be a breakthrough in cancer research. The objective of this research is to conduct basic in-vitro and in-vivo studies to understand the underlying physics of drug-loaded magneto-electric nanoparticles (MENs) at highly localized tumor sites. The engineering approach lies in increasing the porosity of the cell membrane, via application of a low-energy magnetic field, to allow the drug to penetrate inside the cancer cells without affecting the surrounding healthy cells. The proposed approach will form a basis of a novel external-field-controlled procedure to treat various cancers, including ovarian, breast and lung. An important goal of the project is to motivate students, especially underrepresented minorities at FIU and in South Florida, to pursue cross-disciplinary degrees at the intersection of nano-engineering and medicine. The interdisciplinary research team includes an electrical engineer, a gynecologic oncologist, a clinical pharmacologist and a cellular biologist. In ovarian cancers, intraperitoneal delivery through a surgically implanted catheter has shown improved survival rates. However, catheter complications and toxicity have precluded widespread adoption of this technique. In this study, a new nanotechnology is proposed to take advantage of (i) the difference between the membrane electric properties of cancer and healthy cells, and (ii) the capability of magneto-electric nanoparticles (MENs) at body-temperature to serve as localized converters of a remotely supplied magnetic field into the MENs' intrinsic electric fields that can trigger local nano-electroporation effects. The technique allows to remotely control the electric fields in the vicinity of intravenously injected MENs-loaded drug and consequently to enable drug delivery with required specificity to the tumor cells. Electroporation will be used to deliver a drug inside the cytosol via application of high enough electric field to overcome the threshold required for increasing the porosity for drug penetration inside the cell. The required specificity is due to the lower threshold of the cancer cells being by at least a factor of two than that of the healthy cells. Scanning probe microscopy and comprehensive surface spectroscopy will be used to understand the pharmacokinetics and pharmacodynamics of the MENs' interaction with both the cancer and healthy cellular microenvironment under different field conditions. Ovarian cancer will be used as a model with nanoparticles core shell of cobalt iron titanate and barium titatnate as basic MENs in conjunction with paclitaxel as a popular mitotic inhibitor drug. Standard assays will be used to study the MENs' toxicity under different field conditions. A mouse animal model will be exploited to conduct in-vivo studies.

date/time interval

  • June 1, 2014 - May 31, 2018

sponsor award ID

  • 1408063

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