Prof. Rinaldi’s research interests are in biomedical applications of magnetic nanoparticles, including applications where the particles respond to magnetic fields by rotating, exerting forces/torques on biological structures, or dissipating the energy of the magnetic field in the form of heat. Prof. Rinaldi is also interested in the fundamental fluid physics of magnetic nanoparticle suspensions, commonly referred to as ferrofluids, and of magnetic soft matter. Work in Prof. Rinaldi’s laboratory spans theory and simulation to study magnetic nanoparticle response to time varying magnetic fields, nanoparticle synthesis and modification, characterization of nanoparticle physical, chemical, and magnetic properties, and testing the interactions of magnetic nanoparticles with cells and tissues.
Contributions to 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 various ferrofluids. Rinaldi’s group has also developed simulation methods to test continuum-level phenomenological models in ways that are currently not possible through experiments.
- Arlex Chaves and Carlos Rinaldi, “Interfacial Stress Balances in Structured Continua and Free Surface Flows in Ferrofluids.” Physics of Fluids, 26:042101, 2014.
- Isaac Torres-Diaz, Angelica Cortes, Yarilyn Cedeño-Mattei, Oscar Perales-Perez, and Carlos Rinaldi, “Flows and torques in Brownian ferrofluids subjected to rotating uniform magnetic fields in a cylindrical and annular geometry.” Physics of Fluids, 26:012004, 2014.
- Denisse Soto-Aquino and Carlos Rinaldi, “Magnetoviscosity in dilute ferrofluids from rotational Brownian dynamics simulations.” Physical Review E, 82(4):046310, 2010.
- Arlex Chaves, Markus Zahn, and Carlos Rinaldi, “Spin-up flow of ferrofluids: Asymptotic theory and experimental measurements.” Physics of Fluids, 20:053102, 2008.
Development of magnetic measurement tools to assess the environment surrounding magnetic nanoparticles: From the point of view of fluid mechanics, 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. Microrheology has led to advances in understanding the properties of complex and biological fluids at the microscale. However, understanding of nanoscale mechanical properties remains limited due to a lack of suitable tools. Rinaldi’s group has developed a technique to assess mechanical properties of fluids using magnetic nanoparticles (~10-20 nm diameter) as probes. This technique 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 probing the mechanical properties of complex and biological fluids at the nanoscale.
- Rishit R. Merchant, Lorena P. Maldonado-Camargo, and Carlos Rinaldi, “In situ measurements of dispersed and continuous phase viscosities of emulsions using nanoparticles.” Journal of Colloid and Interface Science, 486:241-248,
- Lorena P. Maldonado-Camargo and Carlos Rinaldi, “Breakdown of the Stokes-Einstein relation for the rotational diffusivity of polymer grafted nanoparticles in polymer melts.” Nano Letters, 16:6767-6773, 2016.
- Ana C. Bohorquez and Carlos Rinaldi, “In situ evaluation of nanoparticle-protein interactions by dynamic magnetic susceptibility measurements,” Particle & Particle Systems Characterization, 31(5):561-570,
- Victoria L. Calero, Darlene I. Santiago, and Carlos Rinaldi, “Quantitative nanoscale viscosity measurements using magnetic nanoparticles and SQUID AC susceptibility measurements.” Soft Matter, 7(9):4497-4503, 2011.
Development of magnetic nanoparticles that are colloidally stable in biological environments: Although magnetic nanoparticles have been synthesized since the 1960’s, even as late as 2009 most methods to obtain aqueous-phase nanoparticles resulted in rapid aggregation and precipitation in biological environments and in cell culture media. This phenomenon seriously confounded studies of nanoparticle interactions with cells and of their biodistribution. Rinaldi’s group was among the first to realize that one of the major contributors to this problem was displacement of physisorbed coatings by species present in biological milieu. Inexpensive and scalable methods were adapted to coat magnetic nanoparticles with covalently grafted layers of polysaccharides and polymers, and their superior colloidal stability in biological environments was demonstrated through a combination of modeling and experimentation. These nanoparticles possess predictable physicochemical properties, facilitating rational design and interpretation of studies of their interactions with cells and tissues.
- Lenibel Santiago-Rodríguez, Moises Montalvo-Lafontaine, Cristian Castro, Janet Méndez-Vega, Magda Latorre-Esteves, Eduardo J. Juan, Edna Mora, Madeline Torres-Lugo, and Carlos Rinaldi, “Synthesis, Stability, Cellular Uptake, and Blood Circulation Time of Carboxymethyl-Inulin Coated Magnetic Nanoparticles.” Journal of Materials Chemistry B, 1:2807-2817, 2013. (PMCID: PMC3731157)
- Carola Barrera, Adriana P. Herrera, Nayla Bezares, Esteban Fachini, Juan P. Hinestroza, and Carlos Rinaldi, “Effect of poly(ethylene oxide) graft molecular weight on the colloidal properties of iron oxide nanoparticles for biomedical pplications.” Journal of Colloid and Interface Science, 377:40-50, 2012.
- Mar Creixell, Adriana P. Herrera, Magda Latorre-Esteves, Vanessa Ayala, Madeline Torres-Lugo, and Carlos Rinaldi, “The effect of graft method on the stability and cytotoxicity of carboxymethyl dextran coated magnetic nanoparticles.” Journal of Materials Chemistry, 20:8539-8547, 2010.
- Carola Barrera, Adriana P. Herrera, and Carlos Rinaldi, “Colloidal dispersions of monodisperse magnetite nanoparticles modified with poly(ethylene glycol).” Journal of Colloid and Interface Science, 329:107-113, 2009.
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, Rinald’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. These findings are transforming the field of magnetic nanoparticle thermal therapy.
- Nicole Iovino, Ana C. Bohorquez, and Carlos Rinaldi, “Magnetic nanoparticle targeting of lysosomes: a viable method of overcoming tumor resistance?” Nanomedicine, 9(7):937-939, 2014.
- Maribella Domenech, Ileana Marrero-Berrios, Madeline Torres-Lugo, and Carlos Rinaldi, “Lysosomal Membrane Permeabilization by Targeted Magnetic Nanoparticles in Alternating Magnetic Fields.” ACS Nano, 7(6):5091-5101, 2013.
- Liliana Polo-Corrales and Carlos Rinaldi, “Monitoring iron oxide nanoparticle surface temperature in an alternating magnetic field using thermoresponsive-fluorescent polymers.” Journal of Applied Physics, 111:07B334, 2012.
- Mar Creixell, Ana C. Bohorquez, Madeline Torres-Lugo, and Carlos Rinaldi, “EGFR-targeted magnetic nanoparticle heaters can kill cancer cells without a perceptible temperature rise.” ACS Nano, 5(9), 7124-7129, 2011.
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. Prof. 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.
- Merlis Alvarez-Berrios, Angel Castillo, Carlos Rinaldi, and Madeline Torres-Lugo, “Enhanced proteotoxic stress: one of the contributors for hyperthermic potentiation of the proteasome inhibitor bortezomib using magnetic nanoparticles,” Biomaterials Science, 3:391-400,
- Merlis Alvarez-Berrios, Angel Castillo, Carlos Rinaldi, and Madeline Torres-Lugo, “Magnetic fluid hyperthermia enhances bortezomib cytotoxicity in sensitive and resistant cancer cells lines,” International Journal of Nanomedicine, 9:145-153, 2014. (PMCID: PMC3873208)
- Merlis Alvarez-Berrios, Angel Castillo, Jose Mendéz, Orlando Soto, Carlos Rinaldi, and Madeline Torres-Lugo, “Hyperthermic potentiation of cisplatin by magnetic nanoparticle heaters is correlated with an increase in cell membrane fluidity.” International Journal of Nanomedicine, 2013(8): 1003-1013, 2013. (PMCID: PMC3593770)
- Jason S. Lee, Hector L. Rodríguez-Luccioni, Anil K. Sood, Gabriel Lopez-Berestein, Carlos Rinaldi, and Madeline Torres-Lugo, “Hyperthermia induced by magnetic nanoparticles improves the effectiveness of the anticancer drug cis-diamminedichloroplatinum.” Journal of Nanoscience and Nanotechnology, 11:4153-4157, 2011.