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Kim, Sung Yeol,Kim, Kwang-Min,Hoffman-Kim, Diane,Song, Hyun-Kon,Palmore, G. Tayhas R. American Chemical Society 2011 ACS APPLIED MATERIALS & INTERFACES Vol.3 No.1
<P>Tailoring cell response on an electrode is essential in the application of neural interfaces. In this paper a method of controlling neuron adhesion on the surface of an electrode was demonstrated using conducting polymer composite as an electrode coating. The electrodeposited coating was functionalized further with biomolecules-of-interest (BOI) with their surface concentration controlled via repetition of carbodiimide chemistry. The result was an electrode surface that promoted localized adhesion of primary neurons the density of which could be controlled quantitatively via changes in the number of layers of BOI added. Important to neural interfaces, it was found that additional layers of BOI caused an insignificant increase in the electrical impedance, especially when compared to the large drop in impedance upon coating of the electrode with conducting polymer composite.</P>
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.
Kim, S.,Hoffman, Gregory R.,Poulogiannis, G.,Buel, Gwen R.,Jang, Y.,Lee, K.,Kim, B.Y.,Erikson, Raymond L.,Cantley, Lewis C.,Choo, Andrew Y.,Blenis, J. Cell Press 2013 Molecular cell Vol.49 No.1
The metabolism of glucose and glutamine, primary carbon sources utilized by mitochondria to generate energy and macromolecules for cell growth, is directly regulated by mTORC1. We show that glucose and glutamine, by supplying carbons to the TCA cycle to produce ATP, positively feed back to mTORC1 through an AMPK-, TSC½-, and Rag-independent mechanism by regulating mTORC1 assembly and its lysosomal localization. We discovered that the ATP-dependent TTT-RUVBL½ complex was disassembled and repressed by energy depletion, resulting in its decreased interaction with mTOR. The TTT-RUVBL complex was necessary for the interaction between mTORC1 and Rag and formation of mTORC1 obligate dimers. In cancer tissues, TTT-RUVBL complex mRNAs were elevated and positively correlated with transcripts encoding proteins of anabolic metabolism and mitochondrial function-all mTORC1-regulated processes. Thus, the TTT-RUVBL½ complex responds to the cell's metabolic state, directly regulating the functional assembly of mTORC1 and indirectly controlling the nutrient signal from Rags to mTORC1.
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>
P53 Impairs Endothelium-Dependent Vasomotor Function Through Transcriptional Upregulation of P66shc
Kim, Cuk-Seong,Jung, Saet-Byel,Naqvi, Asma,Hoffman, Timothy A.,DeRicco, Jeremy,Yamamori, Tohru,Cole, Marsha P.,Jeon, Byeong-Hwa,Irani, Kaikobad Ovid Technologies Wolters Kluwer -American Heart A 2008 Circulation research Vol.103 No.12
<P>The transcription factor, p53, and the adaptor protein, p66shc, both play essential roles in promoting oxidative stress in the vascular system. However, the relationship between the two in the context of endothelium-dependent vascular tone is unknown. Here, we report a novel, evolutionarily conserved, p53-mediated transcriptional mechanism that regulates p66shc expression and identify p53 as an important determinant of endothelium-dependent vasomotor function. We provide evidence of a p53 response element in the promoter of p66shc and show that angiotensin II-induced upregulation of p66shc in endothelial cells is dependent on p53. In addition, we demonstrate that downregulation of p66shc expression, as well as inhibition of p53 function in mice, mitigates angiotensin II-induced impairment of endothelium-dependent vasorelaxation, decrease in bioavailable nitric oxide, and hypertension. These findings reveal a novel p53-dependent transcriptional mechanism for the regulation of p66shc expression that is operative in the vascular endothelium and suggest that this mechanism is important in impairing endothelium-dependent vascular relaxation.</P>
( Seongmin Kim ),( Kyung Jin Min ),( Jin Hwa Hong ),( Jae Yun Song ),( Jae Kwan Lee ),( Nak Woo Lee ),( Robert M. Hoffman ),( Sanghoon Lee ) 대한산부인과학회 2018 대한산부인과학회 학술대회 Vol.104 No.-
Objective: Dendropanax morbifera (DM) and Commersonia bartramia (CB) are possible candidates for immunotherapy. In this study, the cytotoxicity and chemical sensitization of DM and CB extracts on gynecologic and colon cancers were evaluated. Methods: The malignant cell lines were cultured and analyzed for cytotoxicity and chemical sensitization. A mouse model was also constructed to make the condition similar to in vivo. Reverse transcription-polymerase chain reaction was conducted to determine alterations in drug-resistant genes. Results: The extracts from DM and CB showed specific cytotoxicity to malignant cell lines. DM increased chemical sensitivity to cervical and ovarian cancer, while CB showed improved sensitization to endometrial cancer. The effects of the extracts were confirmed using a mouse model. The extracts induced differences in the expression levels of a number of genes related to drug resistance. Conclusion: DM and CB extracts could be novel agents for immunotherapy and chemical sensitization in gynecologic and colon cancers. Acknowledgements: This study was supported by Metibio, Inc.
Effect of Substrate Temperature on Residual Stress of ZnO Thin Films Prepared by Ion Beam Deposition
Ju-Won Jeon,Myoung Kim,장이운,J. L. Hoffman,Peter Kim,In-Hwan Lee 대한금속·재료학회 2012 ELECTRONIC MATERIALS LETTERS Vol.8 No.1
We have investigated the effect of substrate temperature on micro-structural properties of ZnO thin films prepared by ion beam deposition technique. ZnO thin films were deposited on AlN-buffered Si (111) and sapphire (001) substrates at various substrate temperatures. The structural properties and surface morphologies were examined by high resolution X-ray diffraction (XRD) and field emission scanning electron microscopy,respectively. The RMS roughness was measured by atomic force microscopy. XRD measurements confirmed that the ZnO thin films were grown well on the AlN-buffered Si (111) and sapphire (001) substrates along the c-axis. Minimization of residual stress was carried out by tuning the substrate temperature. The structural properties were notably improved with increasing substrate temperature.