John Klier, Chair, Chemical Engineering
Sarah Perry, Member, Chemical Engineering
Laura Bradley, Outside Member, Polymer Science & Engineering:
From sunscreen to soap and paint to cancer therapies, nanoparticles are found in our everyday lives. Nanoparticles,because of their large surface area to volume ratio, are ideal candidates forsurface modification and, therefore, implementation in functional materials. Particles are often decorated with chemical moietiesthat enable bindingto specific targets in a wide range of applications. For coatingsystems, such as paint, polymer particles can be designed to interact with pigment to improve opticalproperties and reduce environmental impact.In drug delivery, nanotherapeutics may be modifiedto localize drug molecules in cancerous tissuethereby maximizing therapeutic efficacy while minimizing side effects. In this thesis,nanoparticle systems were functionalized for two applications: 1) encapsulation and dispersion of pigment incoatings, and 2) targeting oftumors using bacteria as a homingbeacon.
As the coating industry continues to transition from solvent-borne to waterborne systems,components of coatingformulations must be intelligently designed to function in aqueousenvironments. Such systems commonly utilize surfactantto functionalize nanoparticles. Surfactant in these systems typically have aKrafft Temperature at or below roomtemperature, meaning solubility is sufficiently high for formation of micelles.Consequently, surfactant molecules caneasily migrate between the surface of particles and the aqueous and micellarphases; imparted functionality is thus transient, and film properties are compromised. Here, hydrophobic surfactant well below its Krafft Temperature is applied in waterborne coatings. Through a facileheating and mixing process, we have successfully functionalized polymer nanoparticles and subsequently encapsulated inorganic pigment. Resultingcoatings exhibit improvedpigment dispersion and opacity which could improvewater barrier properties and reduce overallenvironmental impact and cost of formulations.Systematic studies were performed to verify adsorption of hydrophobicsurfactant onto nanoparticle surfaces,encapsulation of pigment, and improvement of coating opacity via pigmentdispersion. The approach provides asimple, effective, and inexpensive method of noncovalent functionalizationwhich can be broadly applied in aqueous- based colloids.
In 2018, 9.5 million people succumbed to cancer worldwide, and forecastspredict this number will rise to 16.3 million by 2040. Massiveefforts have been directed towardsimproving cancer treatment and therefore patientprognosis. Cleverly, scientists have developed functional nanoparticle-drug platforms that bind to specific receptorsand chemistries found in tumorsto maximize therapeutic efficacy. However, targetedtherapies are limitedby inconsistent biochemistries from patient to patient and cancer to cancer. Attempts toselectively localize particles in tumors while avoiding healthy tissue has proved unsuccessful in clinicaltrials. Therefore, a nanoparticle therapy that effectively targets a wide rangeof cancers is a holy grail in thefield of drug delivery. In this work, a novel bacteria-nanoparticle modalitywas developed and implemented both in vitro andin vivo. Salmonella, which naturally colonizecancer tissue at levels 10,000-fold higher than healthytissue, were intentionally administered to tumors and allowed to proliferate.Colonization of tumors with Salmonellaprovided a distincttarget, or beacon,within cancerous tissue.Nanoparticles were engineered to bind to unique chemistries on the surface of bacteriatherefore allowing for specific accumulation in tumors. In a mouse model, the bacteria-particle therapy achieved2.1-fold higher accumulation in tumors compared to a nonfunctionalized control system.The therapy could provide auniversal treatment for a broadspectrum of cancer types and patients worldwide.