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        Hybrid Nanoparticles for Detection and Treatment of Cancer

        Sailor, Michael J.,Park, Ji‐,Ho WILEY‐VCH Verlag 2012 Advanced Materials Vol.24 No.28

        <P><B>Abstract</B></P><P>There is currently considerable effort to incorporate both diagnostic and therapeutic functions into a single nanoscale system for the more effective treatment of cancer. Nanoparticles have great potential to achieve such dual functions, particularly if more than one type of nanostructure can be incorporated in a nanoassembly, referred to in this review as a hybrid nanoparticle. Here we review recent developments in the synthesis and evaluation of such hybrid nanoparticles based on two design strategies (barge vs. tanker), in which liposomal, micellar, porous silica, polymeric, viral, noble metal, and nanotube systems are incorporated either within (barge) or at the surface of (tanker) a nanoparticle. We highlight the design factors that should be considered to obtain effective nanodevices for cancer detection and treatment.</P>

      • Investigation of grafted mesoporous silicon sponge using hyperpolarized <sup>129</sup>Xe NMR spectroscopy

        Mao, Yougang,Kim, Dokyoung,Hopson, Russell,Sailor, Michael J.,Wang, Li-Qiong Cambridge University Press (Materials Research Soc 2018 Journal of materials research Vol.33 No.17

        <▼1><B>Abstract</B><P/></▼1><▼2><P>Temperature-dependent (173-373 K) hyperpolarized <SUP>129</SUP>Xe nuclear magnetic resonance (<SUP>129</SUP>Xe NMR) analyses along with transmission electron microscopy and N2 adsorption measurements have been applied to understand pore structure and interconnectivity of bare and grafted mesoporous silicon sponge (MSS) materials. The Xe NMR chemical shift data indicate the existence of micropores inside the larger mesopore channels and the effects of grafting on the pore surfaces. The grafted layer estimated at 2 nm in thickness blocks the micropores on the surfaces of mesoporous channels. Partitioning of Xe between the micropores and the mesopores in the MSS materials is temperature-dependent, with Xe principally occupying the micropores at lower temperatures. In addition, the temperature-dependent Xe peak shift of MSS materials verifies the increased uniformity and interconnectivity of mesopores after surface grafting. The results from this study provide useful information for design and development of novel materials.</P></▼2>

      • A regression approach for estimation of anthropogenic heat flux based on a bottom-up air pollutant emission database

        Lee, S.H.,McKeen, S.A.,Sailor, D.J. Pergamon Press ; Elsevier [distribution] 2014 Atmospheric environment Vol.95 No.-

        A statistical regression method is presented for estimating hourly anthropogenic heat flux (AHF) using an anthropogenic pollutant emission inventory for use in mesoscale meteorological and air-quality modeling. Based on bottom-up AHF estimated from detailed energy consumption data and anthropogenic pollutant emissions of carbon monoxide (CO) and nitrogen oxides (NO<SUB>x</SUB>) in the US National Emission Inventory year 2005 (NEI-2005), a robust regression relation between the AHF and the pollutant emissions is obtained for Houston. This relation is a combination of two power functions (Y = aX<SUP>b</SUP>) relating CO and NO<SUB>x</SUB> emissions to AHF, giving a determinant coefficient (R<SUP>2</SUP>) of 0.72. The AHF for Houston derived from the regression relation has high temporal (R = 0.91) and spatial (R = 0.83) correlations with the bottom-up AHF. Hourly AHF for the whole US in summer is estimated by applying the regression relation to the NEI-2005 summer pollutant emissions with a high spatial resolution of 4-km. The summer daily mean AHF range 10-40 W m<SUP>-2</SUP> on a 4 x 4 km<SUP>2</SUP> grid scale with maximum heat fluxes of 50-140 W m<SUP>-2</SUP> for major US cities. The AHFs derived from the regression relations between the bottom-up AHF and either CO or NO<SUB>x</SUB> emissions show a small difference of less than 5% (4.7 W m<SUP>-2</SUP>) in city-scale daily mean AHF, and similar R<SUP>2</SUP> statistics, compared to results from their combination. Thus, emissions of either species can be used to estimate AHF in the US cities. An hourly AHF inventory at 4 x 4 km<SUP>2</SUP> resolution over the entire US based on the combined regression is derived and made publicly available for use in mesoscale numerical modeling.

      • <i>In Vivo</i> Clearance and Toxicity of Monodisperse Iron Oxide Nanocrystals

        Gu, Luo,Fang, Ronnie H.,Sailor, Michael J.,Park, Ji-Ho American Chemical Society 2012 ACS NANO Vol.6 No.6

        <P>Thermal decomposition of organometallic precursors has been found to generate highly crystalline iron oxide (IO) nanocrystals that display superior MR contrast and lower polydispersity than IO nanocrystals synthesized by aqueous precipitation. In the present study, the <I>in vivo</I> characteristics of IO nanocrystals prepared by the thermal decomposition route and then coated with a phospholipid containing a pendant poly(ethylene glycol) chain are examined. The size and surface chemistry of the IO nanocrystal influence the biodistibution, the rate of biodegradation and bioclearance, and the biodegradation products. We conclude that the <I>in vivo</I> fate of PEGylated monodisperse IO nanocrystals and the iron, phospholipid, and oleic acid biodegradation products may influence the cellular environments in the organs and blood that can determine their safety in the body.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/ancac3/2012/ancac3.2012.6.issue-6/nn300456z/production/images/medium/nn-2012-00456z_0003.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/nn300456z'>ACS Electronic Supporting Info</A></P>

      • Thermolytic Grafting of Polystyrene to Porous Silicon

        Wang, Joanna,Joo, Jinmyoung,Kennard, Rhiannon M.,Lee, Sang-Wha,Sailor, Michael J. American Chemical Society 2016 Chemistry of materials Vol.28 No.1

        <P>Inert-atmosphere thermolysis of polystyrene, preloaded into a porous silicon (pSi) template, generates a composite in which styrenic fragments are chemically grafted via Si C bonds to the surface of the pore walls. The quantity of styrenic material in the pores, and thus the final porosity of the composites, is controlled by the amount of polystyrene initially loaded into the pSi host and the time and temperature of thermolysis. For a host template with a porosity of 64 +/- 1%, the porosity of the resulting composite can be varied from 10 to 50%. The composites are significantly more hydrophobic than bulk polystyrene, displaying water contact angles ranging from 110 to 138 degrees compared to a value of 89 for a pure polystyrene film. The contact angle follows the Cassie rule for porosity values up to 40%, increasing with increasing porosity. For composite porosity values >40%, the contact angle is observed to decrease, and this correlates with increasing silicon oxide content and a decrease in hydrophobicity. The stability of the grafted composite material in aqueous base (>pH 12) is enhanced with increasing styrenic content.</P>

      • A Stable, Label-free Optical Interferometric Biosensor Based on TiO<sub>2</sub> Nanotube Arrays

        Mun, Kyu-Shik,Alvarez, Sara D.,Choi, Won-Youl,Sailor, Michael J. American Chemical Society 2010 ACS NANO Vol.4 No.4

        <P>Optical interferometry of a thin film array of titanium dioxide (TiO<SUB>2</SUB>) nanotubes allows the label-free sensing of rabbit immunoglobulin G (IgG). A protein A capture probe is used, which is immobilized on the inner pore walls of the nanotubes by electrostatic adsorption. Control experiments using IgG from chicken (which does not bind to protein A) confirms the specificity of the protein A-modified TiO<SUB>2</SUB> nanotube array sensor. The aqueous stability of the TiO<SUB>2</SUB> nanotube array was examined and compared with porous silica (SiO<SUB>2</SUB>), a more extensively studied thin film optical biosensor. The TiO<SUB>2</SUB> nanotube array is stable in the pH range 2 to 12, whereas the porous SiO<SUB>2</SUB> sensor displays significant degradation at pH > 8.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/ancac3/2010/ancac3.2010.4.issue-4/nn901312f/production/images/medium/nn-2009-01312f_0002.gif'></P>

      • Gated Luminescence Imaging of Silicon Nanoparticles

        Joo, Jinmyoung,Liu, Xiangyou,Kotamraju, Venkata Ramana,Ruoslahti, Erkki,Nam, Yoonkey,Sailor, Michael J. American Chemical Society 2015 ACS NANO Vol.9 No.6

        <P>The luminescence lifetime of nanocrystalline silicon is typically on the order of microseconds, significantly longer than the nanosecond lifetimes exhibited by fluorescent molecules naturally present in cells and tissues. Time-gated imaging, where the image is acquired at a time after termination of an excitation pulse, allows discrimination of a silicon nanoparticle probe from these endogenous signals. Because of the microsecond time scale for silicon emission, time-gated imaging is relatively simple to implement for this biocompatible and nontoxic probe. Here a time-gated system with ∼10 ns resolution is described, using an intensified CCD camera and pulsed LED or laser excitation sources. The method is demonstrated by tracking the fate of mesoporous silicon nanoparticles containing the tumor-targeting peptide iRGD, administered by retro-orbital injection into live mice. Imaging of such systemically administered nanoparticles <I>in vivo</I> is particularly challenging because of the low concentration of probe in the targeted tissues and relatively high background signals from tissue autofluorescence. Contrast improvements of >100-fold (relative to steady-state imaging) is demonstrated in the targeted tissues.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/ancac3/2015/ancac3.2015.9.issue-6/acsnano.5b01594/production/images/medium/nn-2015-01594r_0004.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/nn5b01594'>ACS Electronic Supporting Info</A></P>

      • Close Correlation of Monoamine Oxidase Activity with Progress of Alzheimer’s Disease in Mice, Observed by <i>in Vivo</i> Two-Photon Imaging

        Kim, Dokyoung,Baik, Sung Hoon,Kang, Seokjo,Cho, Seo Won,Bae, Juryang,Cha, Moon-Yong,Sailor, Michael J.,Mook-Jung, Inhee,Ahn, Kyo Han American Chemical Society 2016 ACS central science Vol.2 No.12

        <P>Monoamine oxidases (MAOs) play an important role in Alzheimer's disease (AD) pathology. We report in vivo comonitoring of MAO activity and amyloid-beta (A beta) plaques dependent on the aging of live mice with AD, using a two-photon fluorescence probe. The probe under the catalytic action of MAO produces a dipolar fluorophore that senses A beta plaques, a general AD biomarker, enabling us to comonitor the enzyme activity and the progress of AD indicated by A beta plaques. The results show that the progress of AD has a close correlation with MAO activity, which can be categorized into three stages: slow initiation stage up to three months, an aggressive stage, and a saturation stage from nine months. Histological analysis also reveals elevation of MAO activity around A beta plaques in aged mice. The close correlation between the MAO activity and AD progress observed by in vivo monitoring for the first time prompts us to investigate the enzyme as a potential biomarker of AD.</P>

      • Tumor-Targeting, MicroRNA-Silencing Porous Silicon Nanoparticles for Ovarian Cancer Therapy

        Bertucci, Alessandro,Kim, Kang-Hoon,Kang, Jinyoung,Zuidema, Jonathan M.,Lee, Seo Hyeon,Kwon, Ester J.,Kim, Dokyoung,Howell, Stephen B.,Ricci, Francesco,Ruoslahti, Erkki,Jang, Hyeung-Jin,Sailor, Michae American Chemical Society 2019 ACS APPLIED MATERIALS & INTERFACES Vol.11 No.27

        <P>Silencing of aberrantly expressed microRNAs (miRNAs or miRs) has emerged as one of the strategies for molecular targeted cancer therapeutics. In particular, miR-21 is an oncogenic miRNA overexpressed in many tumors, including ovarian cancer. To achieve efficient administration of anti-miR therapeutics, delivery systems are needed that can ensure local accumulation in the tumor environment, low systemic toxicity, and reduced adverse side effects. In order to develop an improved anti-miR therapeutic agent for the treatment of ovarian cancer, a nanoformulation is engineered that leverages biodegradable porous silicon nanoparticles (pSiNPs) encapsulating an anti-miR-21 locked nucleic acid payload and displaying a tumor-homing peptide for targeted distribution. Targeting efficacy, miR-21 silencing, and anticancer activity are optimized in vitro on a panel of ovarian cancer cell lines, and a formulation of anti-miR-21 in a pSiNP displaying the targeting peptide CGKRK is identified for in vivo evaluation. When this nanoparticulate agent is delivered to mice bearing tumor xenografts, a substantial inhibition of tumor growth is achieved through silencing of miR-21. This study presents the first successful application of tumor-targeted anti-miR porous silicon nanoparticles for the treatment of ovarian cancer in a mouse xenograft model.</P> [FIG OMISSION]</BR>

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