Document Type

Dissertation

Degree

Doctor of Philosophy (PhD)

Department

Medicine

First Advisor's Name

Sakhrat Khizroev

First Advisor's Committee Title

Committee Chair

Second Advisor's Name

Georg Petroianu

Second Advisor's Committee Title

Committee Member

Third Advisor's Name

Stavros V. Georgakopoulos

Third Advisor's Committee Title

Committee Member

Fourth Advisor's Name

Osama A. Mohammed

Fourth Advisor's Committee Title

Committee Member

Fifth Advisor's Name

Carolyn D. Runowicz

Fifth Advisor's Committee Title

Committee Member

Keywords

magnetoelectric nanoparticles, magnetic nanoparticles, personalized medicine, cancer, nanomedicine, nanotechnology, drug delivery, nanoparticle biodistribution

Date of Defense

11-4-2016

Abstract

A major challenge of cancer treatment is successful discrimination of cancer cells from healthy cells. Nanotechnology offers multiple venues for efficient cancer targeting. Magnetoelectric nanoparticles (MENs) are a novel, multifaceted, physics-based cancer treatment platform that enables high specificity cancer targeting and externally controlled loaded drug release. The unique magnetoelectric coupling of MENs allows them to convert externally applied magnetic fields into intrinsic electric signals, which allows MENs to both be drawn magnetically towards the cancer site and to electrically interface with cancer cells. Once internalized, the MEN payload release can be externally triggered with a magnetic field. MENs uniquely allow for discrete manipulation of the drug delivery and drug release mechanisms to allow an unprecedented level of control in cancer targeting. In this study, we demonstrate the physics behind the MEN drug delivery platform, test the MEN drug delivery platform for the first time in a humanized mouse model of cancer, and characterize the biodistribution and clearance of MENs. We found that MENs were able to fully cure the model cancer, which in this case was human ovarian carcinoma treated with paclitaxel. When compared to conventional magnetic nanoparticles and FDA approved organic PLGA nanoparticles, MENs are the highest performing treatment, even in the absence of peripheral active targeting molecules. We also mapped the movement through peripheral organs and established clearance trends of the MENs. The MENs cancer treatment platform has immense potential for future medicine, as it is generalizable, personalizable, and readily traceable in the context of treating essentially any type of cancer.

Identifier

FIDC001249

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