20.109(F12) Pre-Proposal: Engineering Viral Magnetic Nanoparticles for Magnetic Hyperthermic Cancer Therapy

Investigators

• Coyin Oh
• Joanna Yeh
• T/R
• Green

Title of Proposed Project

20.109(F12) Pre-Proposal: Engineering viral magnetic nanoparticles for magnetic hyperthermic cancer therapy

Project Summary

Magnetic hyperthermia is an attractive cancer therapy due to its specificity and low toxicity to healthy tissue. Current magnetic hyperthermia struggles with low heat generation due to low local concentration of magnetic nanoparticles. The goal of the study is to employ complexes composed of phage and magnetic nanoparticles (MNPs) to increase the efficacy of magnetic hyperthermia.

Introduction

The field of magnetic hyperthermia has attracted a lot of attention in the past thirty years as an alternative cancer therapy method. Magnetic hyperthermia proposes the placement of magnetic nanoparticles (MNP) in tumor cells under an alternating magnetic field. Nanoparticles often have unique physical and chemical properties that can be varied based on size and shape. MNPs are no different; these nanoparticles are superparamagnetic, gaining magnetic properties in the presence of a magnetic field. As the direction of the magnetic field alternates, MNPs undergo magnetic hysteresis losses that are dissipated to local surroundings as thermal energy. Targeted sites usually are heated to temperatures between 42 and 45 C to cause cell damage or death. A main challenge to this method is the localization of MNPs to targeted tumor cells. Sometimes MNPs circulate around the bloodstream and do not reach the targeted sites as intended. At times they get internalized and absorbed by the endoplasmic reticulum system of the cells. This low efficiency of MNP transport calls for a higher applied dosage of MNPs in this form of cancer treatment. How can we concentrate MNPs within tumor cells to produce sufficient heat for complete cell apoptosis?

References:

1. A.J. Giustini, A.A. Petryk, S.M. Cassim, J.A. Tate, I. Baker, P.J. Hoopes. Magnetic nanoparticle hyperthermia in cancer treatment. Nano LIFE 2010; 01: 17.
2. D. Ghosh, Y. Lee, S. Thomas, A. G. Kohli, D. S. Yun, A. M. Belcher, K. A. Kelly. M13-templated magnetic nanoparticles for targeted in vivo imaging of prostate cancer. Nat. Nanotechnol. 2012; 7 (10): 677–82.
3. Add more references as deem appropriate

Your idea

Our proposed project aims to use viral magnetic nanoparticles to increase the efficacy of magnetic hyperthermia. Viral MNP complexes consist of MNPs attached to viruses that have minimal harmful effects to humans. While the medical applications of viral MNPs has been studied for over a decade now, their functions have been mostly limited to in vivo MRI imaging and targeted gene delivery. Using viral MNPs, our approach can potentially concentrate MNPs in targeted tumor cells, thereby achieving the level of heat necessary for effective cell apoptosis yet at the same time, lowering the minimum MNP dosage required for the treatment.

The hypothesis is our engineered viral MNPs can increase the current efficacy of magnetic hypothermia. This will be measured in terms of tumor cell death per mass of MNPs used. Our general preliminary approach involves five stages:

Stage 1: Virus Hunt

We need to investigate how our selected virus (which is most likely one of the following: TMV, M13, CCMV, CPMV, BMV or TPMV) interacts with mammalian cells in vivo.

Stage 2: Screening for MNP binding site on virus

We will start by using Fe₃O₄ as our MNP of interest. With this, we need to do a protein coat screen of the selected virus for a protein coat that can bind with our MNP.

Stage 3: Screening for tumor-specific sequence binding site on virus

We need to do a protein coat or RNA screen of the virus for a region that can bind with a tumor-specific peptide sequence. If necessary, we might need to screen tumors for short sequences on their cell surfaces that are unique to tumor cells only.

Stage 4: Virus engineering

We can now engineer wild-type viruses using specific protein coats or RNA regions isolated in Stage 2 and 3 to produce the viral MNP of interest.

Stage 5: in vivo testing

We can now do an in vivo experiment by injecting our viral MNPs into the circulatory system of mice that developed tumors. By subjecting these mice to an alternating magnetic field under standard hyperthermia conditions, and measure the change in tumor size afterwards, we can quantify the efficacy of using viral MNPs in magnetic hypothermia.

A sketch