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      • Facilitated intracellular delivery of peptide-guided nanoparticles in tumor tissues

        Kim, J.H.,Bae, S.M.,Na, M.H.,Shin, H.,Yang, Y.J.,Min, K.H.,Choi, K.Y.,Kim, K.,Park, R.W.,Kwon, I.C.,Lee, B.H.,Hoffman, A.S.,Kim, I.S. Elsevier Science Publishers 2012 Journal of controlled release Vol.157 No.3

        Macromolecular nanoparticles can extravasate and accumulate within tumor tissues via the passive targeting system, reflecting enhanced permeability and the retention effect. However, the unsatisfactory tumor therapeutic efficacy of the passive-targeting system, attributable to the retention of extravasated nanoparticles in the vicinity of tumor vessels, argues that a new system that facilitates intracellular delivery of nanoparticles within tumors is needed. Here, we developed hydrophobically modified glycol chitosan (HGC) nanoparticles conjugated with interleukin-4 receptor (IL-4R) binding peptides, termed I4R, and tested them in mice bearing IL-4R-positive tumors. These HGC-I4R nanoparticles exhibited enhanced IL-4R-dependent cellular uptake in tumors compared to nonconjugated nanoparticles, leading to better therapeutic and imaging efficacy. We conclude that I4R facilitates and enhances cellular uptake of nanoparticles in tumor tissues. This study suggests that the intracelluar uptake of nanoparticles in tumors is an essential factor to consider in designing nanoparticles for tumor-targeted drug delivery and imaging.

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        OH (1720 MHz) MASERS: A MULTIWAVELENGTH STUDY OF THE INTERACTION BETWEEN THE W51C SUPERNOVA REMNANT AND THE W51B STAR FORMING REGION

        Brogan, C. L.,Goss, W. M.,Hunter, T. R.,Richards, A. M. S.,Chandler, C. J.,Lazendic, J. S.,Koo, B.-C.,Hoffman, I. M.,Claussen, M. J. IOP Publishing 2013 The Astrophysical journal Vol.771 No.2

        <P>We present a comprehensive view of the W51B H II region complex and the W51C supernova remnant (SNR) using new radio observations from the VLA, VLBA, MERLIN, JCMT, and CSO along with archival data from Spitzer, ROSAT, ASCA, and Chandra. Our VLA data include the first lambda = 400 cm (74 MHz) continuum image of W51 at high resolution (88 ''). The 400 cm image shows non-thermal emission surrounding the G49.2-0.3 H II region, and a compact source of non-thermal emission (W51B_NT) coincident with the previously-identified OH (1720 MHz) maser spots, non-thermal 21 and 90 cm emission, and a hard X-ray source. W51B_NT falls within the region of high likelihood for the position of TeV gamma-ray emission. Using the VLBA, three OH (1720 MHz) maser spots are detected in the vicinity of W51B_NT with sizes of 60-300 AU and Zeeman effect magnetic field strengths of 1.5-2.2 mG. The multiwavelength data demonstrate that the northern end of the W51B HII region complex has been partly enveloped by the advancing W51C SNR and this interaction explains the presence of W51B_NT and the OH masers. This interaction also appears in the thermal molecular gas which partially encircles W51B_NT and exhibits narrow pre-shock (Delta v similar to 5 km s(-1)) and broad post-shock (Delta v similar to 20 km s(-1)) velocity components. RADEX radiative transfer modeling of these two components yield physical conditions consistent with the passage of a non-dissociative C-type shock. Confirmation of the W51B/W51C interaction provides additional evidence in favor of this region being one of the best candidates for hadronic particle acceleration known thus far.</P>

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        Overview of the 2009 Release of the Evaluated Nuclear Data Library (ENDL2009)

        D. Brown,B. Beck,M. -A. Descalle,R. Hoffman,E. Ormand,P. Navratil,N. Summers,I. Thompson,R. Vogt,W. Younes,R. Barnowski 한국물리학회 2011 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.59 No.23

        The Lawrence Livermore National Laboratory (LLNL) Physics Division has produced the next iteration of LLNL's evaluated nuclear database, ENDL2009. ENDL2009 is the second in a series of major ENDL library releases designed to support LLNL's current and future nuclear data needs. This library includes 585 distinct transport-ready evaluations in the neutron sub-library and many physics improvements for energy, nuclear security and stockpile stewardship. In building this library, we adopted the best of the world's nuclear data efforts including the ENDF/B-VII.0, JENDL and other libraries. A large fraction of the neutron sub-library and all of the charged-particle sub-libraries consist of new evaluations developed at LLNL for the ENDL2009 library. In addition, ENDL2009 supports new features such as energy-dependent Q values from fission, support for unresolved resonances and average momentum deposition. Finally, this release is our most highly tested release as we have strengthened our already rigorous testing regime by adding tests against LANL Activation Ratio Measurements and many new critical assemblies. Our testing is now being incorporated into our development process and is serving to guide database improvements.

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        Poly-paclitaxel/cyclodextrin-SPION nano-assembly for magnetically guided drug delivery system

        Jeon, H.,Kim, J.,Lee, Y.M.,Kim, J.,Choi, H.W.,Lee, J.,Park, H.,Kang, Y.,Kim, I.S.,Lee, B.H.,Hoffman, A.S.,Kim, W.J. Elsevier Science Publishers 2016 Journal of controlled release Vol.231 No.-

        <P>This work demonstrates the development of magnetically guided drug delivery systems and its potential on efficient anticancer therapy. The magnetically guided drug delivery system was successfully developed by utilizing superparamagnetic iron oxide nanoparticle, beta-cyclodextrin, and polymerized paclitaxel. Multivalent host-guest interactions between beta-cyclodextrin-conjugated superparamagnetic iron oxide nanoparticle and polymerized paclitaxel allowed to load the paclitaxel and the nanoparticle into the nano-assembly. Clusterized superparamagnetic iron oxide nanoparticles in the nano-assembly permitted the rapid and efficient targeted drug delivery. Compared to the control groups, the developed nano-assembly showed the enhanced anticancer effects in vivo as well as in vitro. Consequently, the strategy of the use of superparamagnetic nanoparticles and multivalent host-guest interactions has a promising potential for developing the efficient drug delivery systems. (C) 2016 Elsevier B.V. All rights reserved.</P>

      • In vivo imaging of tumor apoptosis using histone H1-targeting peptide

        Wang, K.,Purushotham, S.,Lee, J.Y.,Na, M.H.,Park, H.,Oh, S.J.,Park, R.W.,Park, J.Y.,Lee, E.,Cho, B.C.,Song, M.N.,Baek, M.C.,Kwak, W.,Yoo, J.,Hoffman, A.S.,Oh, Y.K.,Kim, I.S.,Lee, B.H. Elsevier Science Publishers 2010 Journal of controlled release Vol.148 No.3

        In vivo imaging of apoptosis could allow monitoring of tumor response to cancer treatments such as chemotherapy. Using phage display, we identified the CQRPPR peptide, named ApoPep-1(Apoptosis-targeting Peptide-1), that was able to home to apoptotic and necrotic cells in tumor tissue. ApoPep-1 also bound to apoptotic and necrotic cells in culture, while only little binding to live cells was observed. Its binding to apoptotic cells was not dependent on calcium ion and not competed by annexin V. The receptor for ApoPep-1 was identified to be histone H1 that was exposed on the surface of apoptotic cells. In necrotic cells, ApoPep-1 entered the cells and bound to histone H1 in the nucleus. The imaging signals produced during monitoring of tumor apoptosis in response to chemotherapy was enhanced by the homing of a fluorescent dye- or radioisotope-labeled ApoPep-1 to tumor treated with anti-cancer drugs, whereas its uptake of the liver and lung was minimal. These results suggest that ApoPep-1 holds great promise as a probe for in vivo imaging of apoptosis, while histone H1 is a unique molecular signature for this purpose.

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