This award by the Biomaterials Program in the Division of Materials Research to Canisius College is to develop novel fluorine-containing MRI contrast agents based on the use of porous silica nanoparticles. The toxicity of many drugs limits the amount of drug that can be administered, especially for many chemotherapies used to treat cancer. Drug-delivery agents are materials that encapsulate drugs and protect healthy tissue from these potentially negative side-effects. Most drug-delivery agents include modifications that allow the drug-delivery agent, and therefore the drug, to accumulate preferentially at only the diseased tissue, allowing an even greater local dose at the target. State-of-the-art drug-delivery agents also contain imaging agents, such as a dye or contrast agent, that allows for the simultaneous pinpointing of diseased tissue and delivery to it. One imaging agent that has seen minimal use in combined drug-delivery applications is fluorine magnetic resonance imaging (MRI), due to limitations in the delivery vehicle. This project aims to create a new class of multifunctional fluorine MRI contrast agents based on a well known drug-delivery system, porous silica nanoparticles. These materials are like microscopic sponges (made out of the same material as sand) that can be modified with the fluorine agent while simultaneously being loaded with a drug, creating a combined drug-delivery and imaging agent. This research will predominantly be carried out by undergraduate researchers at Canisius College, providing an important training opportunity for young chemists. In addition, this research will also enable collaborations with the nearby Roswell Park Cancer Institute and SUNY University at Buffalo. Finally, this project will impact the broader Buffalo community because of the creation and integration of an activity involving nanoscience with the Summer Science Camp at Canisius College, enhancing STEM education in the region.
Targeted drug-delivery using multifunctional particles, combining choice of therapeutic payload, molecular targeting, biocompatibility, and an imaging agent, has become a major research focus as a means to overcome the limitations of low therapeutic efficacy and toxicity caused by systemic administration of chemotherapeutic drugs for treating cancer. There is currently no drug-delivery agent incorporating a fluorine magnetic resonance imaging (MRI) contrast agent that provides all of these characteristics. The objective of this project is to synthesize fluorine MRI contrast agents based on silica nanoparticles and to identify the factors that maximize the fluorine MR signal using this platform. The PI hypothesizes that fluorine atoms immobilized to porous silica particles using linkers that maximize hydration either through charged groups or short hydrophilic polymers will have sufficient molecular flexibility in aqueous systems to be observable by MRI. If successful, these materials will, for the first time, combine the advantages of porous silica nanoparticles with those of fluorine MRI. This project will support undergraduate researchers who will prepare the materials via organic and inorganic synthesis, providing an important training opportunity for young chemists. These students will also use modern equipment to fully characterize the materials, including electron microscopy and fluorine MR imaging at extramural locations, further enhancing the educational impact. Finally, this project will impact the broader Buffalo community because of the creation and integration of an activity involving nanoscience (colloidal gold nanoparticles) with the Summer Science Camp at Canisius College.
