Novel targeted siRNA-loaded hybrid nanoparticles: preparation, characterization and in vitro evaluation

Background: siRNAs have a high potential for silencing critical molecular pathways that are pathogenic. Nevertheless, their clinical application has been limited by a lack of effective and safe nanotechnology-based delivery system that allows a controlled and safe transfection to cytosol of targeted cells without the associated adverse effects. Our group recently reported a very effective and safe hybrid nanoparticle delivery system composing human IgG and poloxamer-188 for siRNA delivery to cancer cells. However, these nanoparticles need to be optimized in terms of particle size, loading capacity and encapsulation efficiency. In the present study, we explored the effects of certain production parameters on particle size, loading capacity and encapsulation efficiency. Further, to make these nanoparticles more specific in their delivery of siRNA, we conjugated anti-NTSR1-mAb to the surface of these nanoparticles to target NTSR1-overexpressing cancer cells. The mechanism of siRNA release from these antiNTSR1-mAb functionalized nanoparticles was also elucidated. Results: It was demonstrated that the concentration of human IgG in the starting nanoprecipitation medium and the rotation speed of the magnetic stirrer influenced the encapsulation efficiency, loading capacity and the size of the nanoparticles produced. We also successfully transformed these nanoparticles into actively targeted nanoparticles by functionalizing with anti-NTSR1-mAb to specifically target NTSR1-overexpressing cancer cells, hence able to avoid undesired accumulation in normal cells. The mechanism of siRNA release from these nanoparticles was elucidated to be by Fickian diffusion. Using flow cytometry and fluorescence microscopy, we were able to confirm the active involvement of NTSR1 in the uptake of these anti-NTSR1-mAb functionalized hybrid nanoparticles by lung adenocarcinoma cells. Conclusions: This hybrid nanoparticle delivery system can be used as a platform technology for intracellular delivery of siRNAs to NTSR1-overexpressing tumor cells.
Nneka Dim
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Antitumor activity of vorinostat-incorporated nanoparticles against human cholangiocarcinoma cells

Background: The aim of this study is to evaluate the anticancer activity of vorinostat-incorporated nanoparticles (vorinostat-NPs) against HuCC-T1 human cholangiocarcinoma cells. Vorinostat-NPs were fabricated by a nanoprecipitation method using poly(dl-lactide-co-glycolide)/poly(ethylene glycol) copolymer. Results: Vorinostat-NPs exhibited spherical shapes with sizes <100 nm. Vorinostat-NPs have anticancer activity similar to that of vorinostat in vitro. Vorinostat-NPs as well as vorinostat itself increased acetylation of histone-H3. Furthermore, vorinostat-NPs have similar effectiveness in the suppression or expression of histone deacetylase, mutant type p53, p21, and PARP/cleaved caspase-3. However, vorinostat-NPs showed improved antitumor activity against HuCC-T1 cancer cell-bearing mice compared to vorinostat, whereas empty nanoparticles had no effect on tumor growth. Furthermore, vorinostat-NPs increased the expression of acetylated histone H3 in tumor tissue and suppressed histone deacetylase (HDAC) expression in vivo. The improved antitumor activity of vorinostat-NPs can be explained by molecular imaging studies using near-infrared (NIR) dye-incorporated nanoparticles, i.e. NIR-dye-incorporated nanoparticles were intensively accumulated in the tumor region rather than normal one. Conclusions: Our results demonstrate that vorinostat and vorinostat-NPs exert anticancer activity against HuCC-T1 cholangiocarcinoma cells by specific inhibition of HDAC expression. Thus, we suggest that vorinostat-NPs are a promising candidate for anticancer chemotherapy in cholangiocarcinoma.Graphical abstractLocal delivery strategy of vorinostat-NPs against cholangiocarcinomas.
Tae Kwak
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Highly Transparent, Nanofiller-Reinforced Scratch-Resistant Polymeric Composite Films Capable of Healing Scratches

ACS Nano

DOI: 10.1021/acsnano.5b03629

Yang Li, Shanshan Chen, Xiang Li, Mengchun Wu and Junqi Sun
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Metal-Enhanced Fluorescence: Wavelength-Dependent Ultrafast Energy Transfer

The Journal of Physical Chemistry C

DOI: 10.1021/acs.jpcc.5b08744

Jaebeom Lee, Sebok Lee, Myungsam Jen and Yoonsoo Pang
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Fast, Ratiometric FRET from Quantum Dot Conjugated Stabilized Single Chain Variable Fragments for Quantitative Botulinum Neurotoxin Sensing

Nano Letters

DOI: 10.1021/acs.nanolett.5b03442

Joonseok Lee, Melissa B. Brennan, Rosemarie Wilton, Clare E. Rowland, Elena A. Rozhkova, Sara Forrester, Daniel C. Hannah, Julia Carlson, Elena V. Shevchenko, Daniel S. Schabacker and Richard D. Schaller
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Conformal Coating Strategy Comprising N-doped Carbon and Conventional Graphene for Achieving Ultrahigh Power and Cyclability of LiFePO4

Nano Letters

DOI: 10.1021/acs.nanolett.5b02604

Kan Zhang, Jeong-Taik Lee, Ping Li, Byoungwoo Kang, Jung Hyun Kim, Gi-Ra Yi and Jong Hyeok Park
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Combining Graphoepitaxy and Electric Fields toward Uniaxial Alignment of Solvent-Annealed Polystyrene–b–Poly(dimethylsiloxane) Block Copolymers

Chemistry of Materials

DOI: 10.1021/acs.chemmater.5b03354

Christine C. Kathrein, Wubin Bai, Jean Anne Currivan-Incorvia, George Liontos, Konstantinos Ntetsikas, Apostolos Avgeropoulos, Alexander Böker, Larisa Tsarkova and Caroline A. Ross
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Cr-Doped TiSe2 – A Layered Dichalcogenide Spin Glass

Chemistry of Materials

DOI: 10.1021/acs.chemmater.5b03091

Huixia Luo, Jason W. Krizan, Elizabeth M. Seibel, Weiwei Xie, Girija S. Sahasrabudhe, Susanna L. Bergman, Brendan F. Phelan, Jing Tao, Zhen Wang, Jiandi Zhang and R. J. Cava
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Strain Tuning of Tin–Halide and Lead–Halide Perovskites: A First-Principles Atomic and Electronic Structure Study

The Journal of Physical Chemistry C

DOI: 10.1021/acs.jpcc.5b07446

Christopher Grote and Robert F. Berger
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Discovering Amorphous Indium Phosphide Nanostructures with High-Temperature ab Initio Molecular Dynamics

The Journal of Physical Chemistry C

DOI: 10.1021/acs.jpcc.5b07264

Qing Zhao, Lisi Xie and Heather J. Kulik
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Fabrication of High-Concentration Aqueous Graphene Suspensions Dispersed by Sodium Lignosulfonate and Its Mechanism

The Journal of Physical Chemistry C

DOI: 10.1021/acs.jpcc.5b06301

Hongming Lou, Duming Zhu, Long Yuan, Xueqing Qiu, Xuliang Lin, Dongjie Yang and Yuan Li
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Interlayer Dependence of G-Modes in Semiconducting Double-Walled Carbon Nanotubes

The Journal of Physical Chemistry C

DOI: 10.1021/acs.jpcc.5b05888

D. I. Levshov, T. Michel, R. Arenal, H. N. Tran, T. X. Than, M. Paillet, Yu. I. Yuzyuk and J.-L. Sauvajol
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Solid–Liquid–Vapor Etching of Semiconductor Nanowires

Nano Letters

DOI: 10.1021/acs.nanolett.5b02880

Ho Yee Hui and Michael A. Filler
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Complex Catalytic Behaviors of CuTiOx Mixed-Oxide during CO Oxidation

The Journal of Physical Chemistry C

DOI: 10.1021/acs.jpcc.5b07099

Hyun You Kim and Ping Liu
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Interplay between Energy-Level Position and Charging Effect of Manganese Phthalocyanines on an Atomically Thin Insulator

ACS Nano

DOI: 10.1021/acsnano.5b03741

Liwei Liu, Thomas Dienel, Roland Widmer and Oliver Gröning
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Watching Atoms Work: Nanocluster Structure and Dynamics

ACS Nano

DOI: 10.1021/acsnano.5b05510

Stephen J. Pennycook, Wu Zhou and Sokrates T. Pantelides
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Crucial Role of Lateral Size for Graphene Oxide in Activating Macrophages and Stimulating Pro-inflammatory Responses in Cells and Animals

ACS Nano

DOI: 10.1021/acsnano.5b04751

Juan Ma, Rui Liu, Xiang Wang, Qian Liu, Yunan Chen, Russell P. Valle, Yi Y. Zuo, Tian Xia and Sijin Liu
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Following the Reactivity of Au25(SC8H9)18– Clusters with Pd2+ and Ag+ Ions Using in Situ X-ray Absorption Spectroscopy: A Tale of Two Metals

The Journal of Physical Chemistry C

DOI: 10.1021/acs.jpcc.5b07945

Atal Shivhare, Kee Eun Lee, Yongfeng Hu and Robert W. J. Scott
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Time-Dependent Density Functional Theory Studies of Optical Properties of Au Nanoparticles: Octahedra, Truncated Octahedra, and Icosahedra

The Journal of Physical Chemistry C

DOI: 10.1021/acs.jpcc.5b05978

Gyun-Tack Bae and Christine M. Aikens
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