by Allison Wang
While Rice University may be famous for its part in the discovery of the buckyball and subsequent Nobel Prize in 1996, the research conducted by our university in the field of nanoparticles extends far beyond that. Roughly on the same size scale as proteins, nanoparticles range from 9 nm to 100 nm and have unique chemical, physical, and biological properties. They can be made from a variety of materials, such as semiconductors, polymers, and metals like gold and iron oxide. (1) Magnetic iron oxide nanoparticles (MIONs), are nanoparticles made out of iron oxides, usually magnetite (Fe3O4) or maghemite (γ-Fe2O3), and are nontoxic to the human body as they are broken down by the liver into iron and oxygen. (1) MIONs have an expanded range of applications for cancer therapy due to their superparamagnetism. When an external magnetic field is applied, the magnetic domains of the MION nanoparticles are synergistically aligned to produce a magnetization that is greater than the individual effects of each particle. (2) This induced magnetism is particularly useful for drug delivery, imaging, and tumor treatment. (1)
Professor Gang Bao, the Department Chair and Foyt Family Professor of Bioengineering and a Professor of Chemistry here at Rice, is the head of one such lab researching the applications of MIONs in different aspects of cancer treatment. He started out working with quantum dots around twenty years ago at the Georgia Institute of Technology and Emory University before being recruited to Rice through CPRIT in 2015. MIONs are able to enhance both the efficiency and specificity of drug delivery to a specific target tissue. The walls of our blood vessels are designed to only let small molecules cross from the bloodstream into the tissue, but by applying an external magnetic field to MIONs present in the circulatory system, the attachments between cells are disrupted. (3) This makes the blood vessel more permeable and allows drugs to extravasate out into bodily tissues. Additionally, by including nanoparticles into therapeutic cells or in the coating layer of drug particles, the applied magnetic field is able to direct the nanoparticle-facilitated treatment toward specific sites of the body. In fact, the nanoparticle surface’s applications in drug delivery can be further specialized to specifically target cancer cells.
By altering the size, surface, and ligands of these nanoparticles, they can be adapted to target specific organs and cells for various applications. For one, the nanoparticles can be used during magnetic resonance imaging (MRI) as a contrast agent. MRIs are produced by applying a strong magnetic field to the body and detecting the spin polarization of hydrogen nuclei with a receiver. The contrasts seen in the MRI image is formed by the magnitude of polarization decaying at different rates in different tissues, which can be further changed through the interaction of the water protons with the nanoparticles. MIONs can also be coated with a radiotracer so that they show up better on fluorescence or PET scans of tumors. (2) By applying a magnetic field directly to a tumor, nanoparticles are attracted to that specific site and help create clearer images of the area. Similar to how nanoparticles can be loaded into drugs to aid with drug delivery, they can also be loaded into cell cultures to assist doctors tracking cells migrating through the body using MRI. (2)This is especially useful for monitoring stem cell treatments and their success. Another important use of nanoparticles lies in their ability to treat cancer through a therapy known as magnetic fluid hyperthermia (MFH), which utilizes the heating of iron oxide nanoparticles to kill or sensitize cancer cells. In MFH, a tumor is injected with nanoparticles and then exposed to an alternating magnetic field that causes the iron oxide to vibrate and generate just enough heat to destroy the cancer cells. (4) This sort of treatment is especially promising for pancreatic cancer; however, research is still ongoing on how to control the energy delivery and avoid non-specific heating of normal tissue.
Currently, the Bao lab is working on synthesizing iron oxide nanoparticles and gaining FDA approval for a small-scale clinical trial. As the field of nanoparticles is still relatively new, there are a lot of challenges that the lab faces before their research can be applied to therapeutic use in a clinic. First and foremost is producing enough particles for use. They currently are synthesizing milligram quantities of the nanoparticles, but the trials needed for FDA approval will require kilograms of nanoparticles. This cannot be achieved by simply scaling up the size of the machine’s reagents and reactions, as doing so would compromise nanoparticle quality. iLISATech, a company founded by Dr. Bao, is attempting to increase the production of iron-oxide nanoparticles to sufficient quantities for clinical trials, as well as for commercialization to sell to other laboratories and companies. Even after they are able to synthesize enough of the nanoparticles, there are still multiple phases and trials required by the FDA before a treatment can be approved for use by the public. As gold particle therapies have already been approved by the FDA, it is just a matter of more time and research before nanoparticle therapies will be approved and implemented in hospitals as a new treatment for cancer.
Works Cited
[1] Wu, W.; et al. Nanoscale Res. Lett. 2008, 3, https://nanoscalereslett.springeropen.com/articles/10.1007/s11671-008-9174-9
[2] Landázuri, N.; et al. Small 2013 , 9(23), 4017-4026.
[3] Qiu, Y. et al. Nat. Commun. [Online] 2017, 8, https://www.nature.com/articles/ncomms15594
[4] Soetaert, F. et al. Adv. Drug Delivery Reviews 2020, 163-164, 65-83.