Folate‐targeted nanoparticles show efficacy in the treatment of inflammatory arthritis

Objective To investigate the uptake of a poly(amidoamine) dendrimer (generation 5 [G5]) nanoparticle covalently conjugated to polyvalent folic acid (FA) as the targeting ligand into macrophages, and to investigate the activity of an FA‐ and methotrexate (MTX)–conjugated dendrimer (G5‐FA‐MTX) as a therapeutic for the inflammatory disease of arthritis. Methods In vitro studies were performed in macrophage cell lines and in isolated mouse macrophages to check the cellular uptake of fluorescence‐tagged G5‐FA nanoparticles, using flow cytometry and confocal microscopy. In vivo studies were conducted in a rat model of collagen‐induced arthritis to evaluate the therapeutic potential of G5‐FA‐MTX. Results Folate‐targeted dendrimer bound and internalized in a receptor‐specific manner into both folate receptor β–expressing macrophage cell lines and primary mouse macrophages. The conjugate G5‐FA‐MTX acted as a potent antiinflammatory agent and reduced arthritis‐induced parameters of inflammation such as ankle swelling, paw volume, cartilage damage, bone resorption, and body weight decrease. Conclusion The use of folate‐targeted nanoparticles to specifically target MTX into macrophages may provide an effective clinical approach for antiinflammatory therapy in rheumatoid arthritis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/86938/1/30459_ftp.pd

CD44v6-Peptide Functionalized Nanoparticles Selectively Bind to Metastatic Cancer Cells

CD44v6 peptide functionalized nanoparticles are fabricated in a facile and controllable way to selectively bind to CD44v6 positive tumor cells with highly efficient anticancer and antimetastatic properties. The reported modular synthesis and facile preparation makes this system highly potent for developing novel multifunctional nanocarriers for therapeutic and/or diagnostic anticancer applications. [Image: see text

Combination Strategies for Targeted Delivery of Nanoparticles for Cancer Therapy

Pharmaceuticals, and more recently biopharmaceuticals, have become the mainstay for antineoplastic treatments in combination with surgical interventions and radiation therapy. In recent years, advances have been made in the development of nano-technological interventions for the treatment of cancer alone or in combination with existing therapeutic modalities. Nanotechnology used for therapeutic drug delivery and sensitization of photodynamic, sonodynamic and radiotherapy are now being tested in preclinical and clinical trials for the treatment of cancer. This article will review the current state of the art for nanotechnology therapies with an emphasis on targeted drug delivery and the observed and likely benefits when used in combination with existing therapeutic approaches

Ocean Heat Transport and the Width of the Hadley Circulation in an Aquaplanet GCM

Thesis (Master's)--University of Washington, 2018Despite decades of research, the fundamental dynamics that govern the width of the Hadley circulation (HC) remain an active area of investigation. This study seeks to further theoretical understanding of HC width and of the mechanisms leading to HC expansion by exploring the response of a zonally-symmetric slab-ocean aquaplanet general circulation model (GCM) to imposed poleward ocean heat transport (OHT). It is found that the presence of OHT causes the HC to extend up to 3° farther into the subtropics than it would in the absence of OHT. This widening of the HC by OHT is interpreted as being driven by a decrease in baroclinicity near the poleward edge of the HC and is decomposed into three components: a decrease in baroclinicity due to (1) a systematic poleward shift of the Intertropical Convergence Zone (ITCZ) throughout the seasonal cycle that drives a decrease in the angular momentum of the HC and, consequently, a weakening of the vertical shear of the zonal wind; (2) an increase in subtropical static stability due to the quasi-moist adiabatic adjustment to warmed subtropical sea surface temperatures (SSTs); and (3) a diabatic relaxation of the meridional SST gradient in the outer tropics and subtropics by OHT. Although mechanism (3) appears contribute the most to the response of HC width to OHT, the contributions from (1) and (2) are by no means negligible (each accounting for up to 20–30% of the HC response). By highlighting the role of ITCZ position in setting the mean width of the HC and in producing HC expansion, a role which has previously been under-appreciated, this study represents an important addition to the existing understanding of theoretical constraints on HC width. Overall, this study indicates a fundamental role for baroclinicity in limiting the poleward extent of the HC

Understanding the spatial distribution of the Southern Hemisphere near-surface westerlies and Its trends

Thesis: S.B., Massachusetts Institute of Technology, Department of Earth, Atmospheric, and Planetary Sciences, 2015.Cataloged from PDF version of thesis.Includes bibliographical references (pages 62-63).In some experiments in which idealized general circulation models (GCMS) are used to study the tropospheric response to stratospheric perturbations, the tropospheric response is much stronger and longer-lived compared to observations (e.g., Polvani and Kushner 2002, Kushner and Polvani 2004). Chan and Plumb (2009) found that those experiments which exhibited particularly long tropospheric decorrelation times (and, by the fluctuation dissipation theorem, much stronger annular mode responses) were marked by bimodality in the distribution of the latitude of surface zonal-mean zonal winds. Here, ERA-Interim and NCEP/NCAR reanalysis data are used to establish if this bimodality exists in the Southern Hemisphere (SH) near-surface winds, which would predict the existence of an additional mode of tropospheric variability exhibiting stronger and longer-lived responses than what has previously been observed. Histograms of the latitudinal position of maximum near-surface zonal-mean zonal winds turn up no convincing evidence of jet bimodality, although they do reveal an interesting - but probably spurious trimodality in the NCEP/NCAR June-August 850-hPa distribution of jet latitude. A climatology of wintertime zonal winds reveals that there is a time-mean split jet over the South Pacific Ocean; furthermore, empirical orthogonal function analysis reveals that, over the South Pacific, the dominant mode of wintertime zonal wind variability is a splitting and un splitting of the jet. Ultimately, both the climatological split jet and its variability are determined not to be evidence of jet bimodality. The temporal trends in the distribution of near-surface jet latitude are also examined. Stratospheric ozone depletion has been implicated in surface circulation changes in the SH high latitudes; one of these changes has been a poleward shift of the jet in austral summer. In this thesis, it is found that a poleward shift of the December-February distribution of jet latitude has taken place from the pre-ozone-hole to ozone-hole eras, consistent with previous findings. The novel result is that there has also been a poleward shift of this distribution in May, which is consistent with a secondary maximum in ozone depletion near the tropopause in April-May as observed by other authors (Thompson et al. 2011), and would imply the occurrence of troposphere-stratosphere coupling in late fall. An in-depth investigation of these May zonal wind trends will be pursued in future work.by Casey C. Hilgenbrink.S.B

Observed Changes in the Southern Hemispheric Circulation in May

Much research has focused on trends in the Southern Hemispheric circulation in austral summer (December–February) in the troposphere and stratosphere, whereas changes in other seasons have received less attention. Here the seasonality and structure of observed changes in tropospheric and stratospheric winds, temperature, and ozone over the Southern Hemisphere are examined. It is found that statistically significant trends similar to those of the Antarctic summer season are also observed since 1979 in austral fall, particularly May, and are strongest over the Pacific sector of the hemisphere. Evidence is provided for a significant shift in the position of the jet in May over the Pacific, and it is shown that the strengthening and shifting of the jet has rendered the latitudinal distribution of upper-tropospheric zonal wind more bimodal. The Antarctic ozone hole has cooled the lower stratosphere and strengthened the polar vortex. While the mechanism and timing are not fully understood, the ozone hole has been identified as a key driver of the summer season tropospheric circulation changes in several previous observational and modeling studies. It is found here that significant ozone depletion and associated polar cooling also occur in the lowermost stratosphere and tropopause region through austral fall, with spatial patterns that are coincident with the observed changes in stratospheric circulation. It is also shown that radiatively driven temperature changes associated with the observed ozone depletion in May represent a substantial portion of the observed May cooling in the lowermost stratosphere, suggesting a potential for contribution to the circulation changes.National Science Foundation (U.S.) (Grant 1419667