Browsing by Author "Pimpinelli, Alberto"

Now showing 1 - 4 of 4
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    A quantitative approach to discover predictors of biodistribution for drug delivery vectors in cancer.
    (2019-04-19) Nizzero, Sara; Nordlander, Peter; Ferrari, Mauro; Pimpinelli, Alberto
    Systemic aspects of cancer simultaneously offer the biggest clinical challenge and the most promising therapeutic niche in the treatment of solid tumors. In fact, treatment often fails in late stages due to the presence of metastasis, a migratory phenotype of cancer invasion. Metastases consist in cancer spread to distant organs which often presents characteristic high levels of heterogeneity and acquired resistance to treatments. Multi-stage injectable delivery vectors have proven powerful in exploiting systemic transport properties connected to physiological parameters to enhance tumor accumulation and directly improve therapeutic efficacy. The theoretical framework in which these concepts first developed is now known by the term transport oncophysics: the study of mass transport phenomena relevant to oncology with a physics-based approach. For injectable inorganic delivery vectors, the major innovation relies on the capability to tailor their organ distribution (biodistribution) upon injection. This capability comes from the controllable design of such systems, which present a discoidal shape with sizes in the micrometer range. While these systems have shown disruptive results in the treatment of triple negative breast cancer metastasis, there is still a lack of fundamental understanding on how patient-specific physiological parameters affect their biodistribution. However, it is well known that patient physiology is often dysregulated in cancer patients. These alterations can be caused by a multitude of reasons: cancer itself, the presence of concurring diseases or conditions, and previous treatment. This patient heterogeneity poses an additional challenge in therapeutic translation of injectable delivery systems. In this work, significant clinically relevant physiological parameters are screened, systematically altered, and quantitatively characterized as transport barriers for systemic delivery. Systematic in vivo biodistribution studies are conducted to address changes in biodistribution resulting from controlled alteration of specific physiological parameters. Uptake kinetic is characterized through time-resolved analysis, and investigated to inform on synergistic relationships among different parameters. A computational approach is then developed to identify a pharmacokinetic (PK) model able to predict the system behavior, and used to investigate the importance of several parameters, and functional relationships. This combined in vivo / in silico approach enables the quantitative description of mechanistic rules that determine the biodistribution of systemically injected delivery vectors. The framework that emerges from this study opens the way to a new paradigm for personalized adaptive therapy, where quantitative measurements, systematic analysis, and mathematical modeling can be combined to investigate and characterize functional relationships between quantitatively characterized physiological parameters and clinically relevant measurables for injectable inorganic delivery vectors.
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    From gas flow to colloidal diffusion: theoretical and experimental investigations of transport in nano- and microchannels, on the ground and in space
    (2018-04-19) Scorrano, Giovanni; Nordlander, Peter; Grattoni, Alessandro; Pimpinelli, Alberto
    Developing predictive models for gas flow through micro- and nanochannels is of great interest in several scientific and technological fields. Existing theories reproduce specific scenarios failing to give solutions that can be applied on a broader spectrum. In this study, we propose a statistical method to predict the flow rate of rarefied gas through rectangular channels based on the distribution of free paths between inter-particle and gas-wall collisions. Our approach can be applied to virtually all geometries, for which the probability distribution of path lengths for gas-wall collisions can be computed, either analytically or by numerical simulations. Additionally, we present a study of nitrogen transport through a wide range of identical slit nanochannels where only the cross section height varies from 250 nm down to 2.5 nm achieving various degrees of gas confinement. The present theoretical model shows excellent agreement with the experimental results demonstrating the validity of our approach.
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    Nanoparticles Heat through Light Localization
    (American Chemical Society, 2014) Hogan, Nathaniel J.; Urban, Alexander S.; Ayala-Orozco, Ciceron; Pimpinelli, Alberto; Nordlander, Peter; Halas, Naomi J.; Laboratory for Nanophotonics; Rice Quantum Institute
    Aqueous solutions containing light-absorbing nanoparticles have recently been shown to produce steam at high efficiencies upon solar illumination, even when the temperature of the bulk fluid volume remains far below its boiling point. Here we show that this phenomenon is due to a collective effect mediated by multiple light scattering from the dispersed nanoparticles. Randomly positioned nanoparticles that both scatter and absorb light are able to concentrate light energy into mesoscale volumes near the illuminated surface of the liquid. The resulting light absorption creates intense localized heating and efficient vaporization of the surrounding liquid. Light trapping-induced localized heating provides the mechanism for low-temperature light-induced steam generation and is consistent with classical heat transfer.
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    Nanoscale studies of CVD graphene and poly(3-hexylthiophene) thin films.
    (2014-04-21) Rai, Chaitra; Kelly, Kevin F.; Pimpinelli, Alberto; Natelson, Douglas; Aazhang, Behnaam
    Transparent solar cell systems have garnered a great deal of attention as possible alternatives to silicon-based solar cells. While conventional silicon-based solar cells absorb solar energy in limited frequency ranges, transparent solar cells absorb solar radiation in both the near infrared and ultraviolet regions of the electromagnetic spectrum. The challenge lies in improving the power conversion efficiency from the current 3.5%. It is therefore crucial to have a complete understanding of the electronic and structural properties of the component materials at the nanoscale to considerably improve their performance. For instance, controlling the morphology and electronic properties of the component acceptor and donor materials will have a direct impact on power conversion efficiencies. In this thesis, I present the use of scanning tunneling microscopy (STM) as a primary tool to analyze these materials with atomic scale resolution. The materials used in this work are monolayer graphene grown by chemical vapor deposition (CVD) and poly(3-hexylthiophene) (P3HT) thin films, which have great potential for use in transparent solar cells. This work outlines my findings in understanding and characterizing different substrate effects on graphene film growth, particularly useful for defect analysis and quality control. This thesis also presents analyses of the important role of pre-treatment of the Cu catalyst on the improvement in quality and continuity of graphene films. Further, this thesis also presents the morphological changes occurring in P3HT film crystallinity resulting from solvent mixing and propose an annealing free approach for efficient self-organization of chains via π-π interactions. I propose the use of two methods for quantifying the persistence length of the polymer chains: edge-detection based Hough transform and the worm-like chain model. By optimizing the graphene electrode and the polymer efficiency we hope to move closer to a carbon-based replacement for bulk semiconductor photovoltaics.