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Carlos Rinaldi is the Chair and Dean’s Leadership Professor in the Department of Chemical Engineering at the University of Florida. He is also a Professor in the J. Crayton Pruitt Family Department of Biomedical Engineering. He received his bachelor’s degree in Chemical Engineering at the University of Puerto Rico, Mayagüez, and completed degrees in Master of Science in Chemical Engineering, Master of Science in Chemical Engineering Practice, and Doctor of Philosophy in Chemical Engineering at the Massachusetts Institute of Technology. Prior to the University of Florida, Dr. Rinaldi was a Professor in the Department of Chemical Engineering at the University of Puerto Rico, Mayagüez. Dr. Rinaldi is a leading scientist in the areas of ferrohydrodynamics, biomedical applications of magnetic nanoparticles, and transport of nanoparticles in complex and biological fluids. His research spans theory and simulation of magnetic nanoparticle response to dynamic magnetic fields, nanoparticle synthesis and surface modification, and characterization of nanoparticle interactions with biological environments. In the field of ferrohydrodynamics, Dr. Rinaldi has made fundamental contributions to understanding of suspension-scale flows of ferrofluids in time-varying and rotating magnetic fields. Through a combination of theoretical and experimental work, his group demonstrated that description of ferrofluid flows in rotating magnetic fields requires consideration of internal angular momentum transport through the so-called couple stress and spin viscosity, unique features in the description of flows of structured continua. In the field of nanomedicine, Dr. Rinaldi has made outstanding contributions to harnessing localized nanoscale heating for magnetic nanoparticle thermal cancer therapy. His group was the first to demonstrate that receptor-targeted nanoparticles can kill cancer cells without a perceptible macroscopic temperature rise through disruption of lysosomes and activation of lysosomal death pathways. He has also contributed to understanding the synergistic interactions of nanoscale thermal therapy and traditional chemotherapeutics. Dr. Rinaldi has pioneered development and application of new methods to evaluate nanoparticle stability and diffusion in complex and biological fluids. Based on non-invasive monitoring of nanoparticle response to oscillating magnetic fields, these methods permit quantitative measurements of nanoparticle aggregation state, hydrodynamic size, and diffusion in complex environments such as polymer melts, polymer solutions, highly-concentrated protein solutions, whole blood, and tissues. More recently, Dr. Rinaldi has contributed to understanding the physics of magnetic nanoparticle response to alternating magnetic fields, enabling rational design of high-sensitivity and high-resolution tracers for magnetic particle imaging, an emerging biomedical imaging technology. Dr. Rinaldi is committed to mentoring new generations of scientists and engineers seeking solutions to biomedical problems and to broadening participation of women and minorities in science and engineering.
Fundamental contributions to understanding the fluid mechanics of magnetic nanoparticle suspensions in time-varying magnetic fields: Ferrofluids, semi-dilute suspensions of magnetic nanoparticles, are fascinating practically relevant examples of fluids that can be manipulated by magnetic fields. Although ferrofluids have been known since the 1960s, we still lack a complete, experimentally validated formulation of their governing equations, limiting our ability engineer novel applications of ferrofluids. Rinaldi has made fundamental contributions to this field through a combination of complementary experimental, theoretical, and simulation approaches. This work led to the demonstration that the description of ferrofluid flows in rotating magnetic fields requires consideration of transport of angular momentum through the so-called couple stress and spin viscosity. Rinaldi’s group was the first to experimentally demonstrate the existence of the spin viscosity and to measure its value for ferrofluids. Rinaldi’s group has also developed simulation methods to test continuum-level phenomenological models in ways that are currently not possible through experiments.
Synthesis and modification of magnetic nanoparticles for biomedical applications: Although magnetic nanoparticles have been synthesized since the 1960’s, most methods to obtain them yield particles with sub-optimal magnetic properties. Furthermore, many formulations intended for use in aqueous-phase result in rapid aggregation and precipitation in biological environments and in cell culture media. These limitations seriously hinder the rational design of magnetic nanoparticles for biomedical applications. Rinaldi’s group has made fundamental contributions to synthesis and modification of magnetic nanoparticles for biomedical applications by developing methods to synthesize nearly defect free particles with optimal magnetic properties and inexpensive and scalable methods to coat magnetic nanoparticles with covalently grafted layers of polysaccharides and polymers. These particles have demonstrated superior colloidal stability in biological environments and possess predictable physicochemical properties, facilitating rational design and interpretation of studies of their interactions with cells and tissues.
Understanding nanoparticle transport in complex fluids and biological environments: The intracellular environment can be described as crowded, complex, and confined, where biomacromolecules with characteristic dimensions of 1-10’s of nm are present at high concentration, and where membranes, organelles, and filamentous matrices restrict motion. Although important in designing nanoparticles for biomedical applications, understanding of the transport of nanoparticles in such environments remains limited. Rinaldi’s group has developed methods based on magnetic measurements that can assess nanoparticle stability and mobility in complex fluid environments, including biological fluids. This approach requires small sample volumes (~20 μl), low concentrations of nanoparticles (~0.02% v/v), and does not require optic access to the sample. Work has demonstrated that this technique is quantitatively accurate, can provide insight into novel nanoscale phenomena, and can be used to assess the interaction of nanoparticles and proteins in situ at physiologically-relevant concentrations. These findings pave the way towards improved understanding of nanoparticle transport in complex fluid environments relevant to biomedical applications.
Harnessing Localized Nanoscale Heating in Nanoparticle Thermal Cancer Therapy: Although initially researchers had imagined that nanoscale heating effects in the vicinity of nanoparticles might be sufficient to damage and kill cells in the absence of a tissue-level temperature rise to the hyperthermia range (43-47°C), the paradigm in the field of nanoparticle thermal cancer therapy since the late 1990s had been that it was impossible to kill cancer cells in this way. Through a combination of magnetic nanoparticle engineering and judicious experimentation, Rinaldi’s research has demonstrated that this paradigm was incorrect and that nanoscale heating phenomena in the vicinity of receptor-targeted magnetic nanoparticles can lead to significant (>99%) reductions in cancer cell clonogenic survival without any macroscopic temperature rise. Furthermore, work has demonstrated that one mechanism responsible for cell death is disruption of nanoparticle-loaded lysosomes, activating lysosomal death pathways that are upregulated in many cancer cells. Furthermore, Rinaldi’s group recently demonstrated the potential of magnetic particle imaging guided magnetic hyperthermia for precise and spatially selective cancer thermal therapy. These findings are transforming the field of magnetic nanoparticle thermal therapy.
Elucidating the Mechanisms Underlying Enhanced Synergy of Magnetic Nanoparticle Hyperthermia and Anti-Cancer Drugs: Hyperthermia (tissue temperature rise to 43-47°C) has been extensively explored in combination with radiotherapy and chemotherapy as a means to enhance treatment outcome, with positive results for some cancer types and treatment combinations. Rinaldi’s studies comparing traditional forms of hyperthermia with hyperthermia induced by magnetic nanoparticles led to hypothesize that localized nanoscale heating in the vicinity of the nanoparticles would cause additional physical damage, resulting in enhanced synergistic effects. Work has demonstrated that this is the case for platinum-based drugs and proteasome inhibitors, and that magnetic nanoparticle hyperthermia significantly re-sensitizes cancer cells with acquired drug resistance to these agents. Furthermore, it has been demonstrated that a variety of mechanisms underlie this enhancement/re-sensitization, including permeabilization/fluidization of the cell membrane, direct damage to microtubules, and increased proteotoxic stress.
Understanding the role of finite relaxation time of magnetic nanoparticles on their heating and magnetic particle imaging performance: The response of biocompatible magnetic nanoparticles to alternating magnetic fields forms the basis of exciting biomedical applications, such as nanoscale magnetic thermal therapy (magnetic hyperthermia), magnetic particle imaging, relaxometric sensing, and magnetically-triggered drug release. In all these applications, understanding the coupling between magnetic, hydrodynamic, thermal, and magnetocrystalline torques on the magnetic nanoparticle dipoles is vital to predict the performance of magnetic nanoparticles. Rinaldi’s group has made fundamental contributions to understanding these phenomena through a combination of theoretical/simulation and experimental approaches. Modeling of rotational Brownian relaxation and internal dipole rotation in the particles has led to understanding of the effect of non-linear magnetization on heat dissipation rates and understanding of the role of relaxation time and mechanism on magnetic particle imaging signal strength and resolution. This understanding is enabling realization of the theranostic potential of magnetic nanoparticles in magnetic particle imaging and hyperthermia applications.
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