High dispersity of carbon nanotubes diminishes immunotoxicity in spleen

Lee, Soyoung,Khang, Dongwoo,Kim, Sang-Hyun Dove Medical Press 2015 INTERNATIONAL JOURNAL OF NANOMEDICINE Vol.10 No.-

<P><B>Background</B></P><P>From the various physiochemical material properties, the chemical functionalization order of single-walled carbon nanotubes (swCNTs) has not been considered as a critical factor for modulating immunological responses and toxicological aspects in drug delivery applications. Although most nanomaterials, including carbon nanotubes, are specifically accumulated in spleen, few studies have focused on spleen immunotoxicity. For this reason, this study demonstrated that the dispersity of swCNTs significantly influenced immunotoxicity in vitro and in vivo.</P><P><B>Materials and methods</B></P><P>For cytotoxicity of swCNTs, MTT assay, reactive oxygen species production, superoxide dismutase activity, cellular uptake, and confocal microscopy were used in macrophages. In the in vivo study, female BALB/c mice were intravenously administered with 1 mg/kg/day of swCNTs for 2 weeks. The body weight, organ weight, hematological change, reverse-transcription polymerase chain reaction, and lymphocyte population were evaluated.</P><P><B>Results</B></P><P>Different orders of chemical functionalization of swCNTs controlled immunotoxicity. In short, less-dispersed swCNTs caused cytotoxicity in macrophages and abnormalities in immune organs such as spleen, whereas highly dispersed swCNTs did not result in immunotoxicity.</P><P><B>Conclusion</B></P><P>This study clarified that increasing carboxyl groups on swCNTs significantly mitigated immunotoxicity in vitro and in vivo. Our findings clarified the effective immunotoxicological factors of swCNTs by increasing dispersity of swCNTs and provided useful guidelines for the effective use of nanomaterials.</P>

Decreased macrophage density on carbon nanotube patterns on polycarbonate urethane

Kim, Jong Youl,Khang, Dongwoo,Lee, Jong Eun,Webster, Thomas J. Wiley Subscription Services, Inc., A Wiley Company 2009 Journal of biomedical materials research. Part A Vol.a88 No.2

<P>Nanotechnology is creating materials that can regenerate numerous tissues (including those used for bone, vascular, cartilage, bladder, and neuronal systems) better than what is currently being implanted. Despite this promise, little is known about the functions of wound healing cells (such as macrophages) on nanomaterials. Carbon nanotubes are intriguing nanomaterials for implantation due to their unique biologically inspired surface, electrical, and mechanical properties. For the above reasons, the objective of the present study was to investigate macrophage function on one promising type of nano-implant material for orthopedic applications (carbon nanotubes microscopically aligned on polymers). To align carbon nanotubes on polymers, a novel imprinting method placing carbon nanotubes in grids of defined spacings (from 30 to 100 μm) on a polymer matrix was developed. In this study, the selective adhesion and proliferation of macrophages after 4 h, 24 h, and 4 days on aligned regions of a currently implanted polymer (specifically, polycarbonate urethane) compared to aligned carbon nanotube patterns were found. That is, decreased macrophage functions were observed in this study on aligned regions of carbon nanotubes compared to polycarbonate urethane. The present in vitro study, thus, provided evidence of the ability of carbon nanotubes to down-regulate macrophage adhesion and proliferation which is important to decrease a harmful persistence wound-healing reaction to orthopedic implants. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res 2009</P>

Multiple cues on the physiochemical, mesenchymal, and intracellular trafficking interactions with nanocarriers to maximize tumor target efficiency

Kim, Sang-Woo,Khang, Dongwoo Dove Medical Press 2015 INTERNATIONAL JOURNAL OF NANOMEDICINE Vol.10 No.-

<P>Over the past 60 years, numerous medical strategies have been employed to overcome neoplasms. In fact, with the exception of lung, bronchial, and pancreatic cancers, the 5-year survival rate of most cancers currently exceeds 70%. However, the quality of life of patients during chemotherapy remains unsatisfactory despite the increase in survival rate. The side effects of current chemotherapies stem from poor target efficiency at tumor sites due to the uncontrolled biodistribution of anticancer agents (ie, conventional or current approved nanodrugs). This review discusses the effective physiochemical factors for determining biodistribution of nanocarriers and, ultimately, increasing tumor-targeting probability by avoiding the reticuloendothelial system. Second, stem cell-conjugated nanotherapeutics was addressed to maximize the tumor searching ability and to inhibit tumor growth. Lastly, physicochemical material properties of anticancer nanodrugs were discussed for targeting cellular organelles with modulation of drug-release time. A better understanding of suggested topics will increase the tumor-targeting ability of anticancer drugs and, ultimately, promote the quality of life of cancer patients during chemotherapy.</P>

Conformational changes of fibrinogen in dispersed carbon nanotubes

Park, Sung Jean,Khang, Dongwoo Dove Medical Press 2012 INTERNATIONAL JOURNAL OF NANOMEDICINE Vol.7 No.-

<P>The conformational changes of plasma protein structures in response to carbon nanotubes are critical for determining the nanotoxicity and blood coagulation effects of carbon nanotubes. In this study, we identified that the functional intensity of carboxyl groups on carbon nanotubes, which correspond to the water dispersity or hydrophilicity of carbon nanotubes, can induce conformational changes in the fibrinogen domains. Also, elevation of carbon nanotube density can alter the secondary structures (ie, helices and beta sheets) of fibrinogen. Furthermore, fibrinogen that had been in contact with the nanoparticle material demonstrated a different pattern of heat denaturation compared with free fibrinogen as a result of a variation in hydrophilicity and concentration of carbon nanotubes. Considering the importance of interactions between carbon nanotubes and plasma proteins in the drug delivery system, this study elucidated the correlation between nanoscale physiochemical material properties of carbon nanotubes and associated structural changes in fibrinogen.</P>

Development of Two-Step Temperature Process to Modulate the Physicochemical Properties of β-lactoglobulin Nanoparticles

Ho-kyung Ha,Gyeong-won Nam,Dongwoo Khang,Sung Jean Park,Mee- Ryung Lee,Won-jae Lee 한국축산식품학회 2017 한국축산식품학회지 Vol.37 No.1

The development of a new manufacturing process, a two-step temperature treatment, to modulate the physicochemical properties of nanoparticles including the size is critical. This is because its physicochemical properties can be key factors affecting the cellular uptake and the bioavailability of bioactive compounds encapsulated in nanoparticles. The aims of this study were to produce (beta-lactoglobulin) β-lg nanoparticles and to understand how two-step temperature treatment could affect the formation and physicochemical properties of β-lg nanoparticles. The morphological and physicochemical properties of β-lg nanoparticles were determined using atomic force microscopy and a particle size analyzer, respectively. Circular dichroism spectroscopy was used to investigate the secondary structure of β-lg. The surface hydrophobicity and free thiol groups of β-lg were increased with a decrease in sub-ambient temperature and an increase in mild heat temperature. As sub-ambient temperature was decreased, a decrease in α-helical content and an increase in β-sheet content were observed. The two-step temperature treatment firstly involved a sub-ambient temperature treatment from 5 to 20ºC for 30 min, followed secondly by a mild heat temperature treatment from 55 to 75ºC for 10 min. This resulted in the production of spherically-shaped particles with a size ranging from 61 to 214 nm. Two-way ANOVA exhibited the finding that both sub-ambient and mild heat temperature significantly (p

Effect of the protein corona on nanoparticles for modulating cytotoxicity and immunotoxicity

Lee, Yeon Kyung,Choi, Eun-Ju,Webster, Thomas J,Kim, Sang-Hyun,Khang, Dongwoo Dove Medical Press 2015 INTERNATIONAL JOURNAL OF NANOMEDICINE Vol.10 No.-

<P>Although the cytotoxicity of nanoparticles (NPs) is greatly influenced by their interactions with blood proteins, toxic effects resulting from blood interactions are often ignored in the development and use of nanostructured biomaterials for in vivo applications. Protein coronas created during the initial reaction with NPs can determine the subsequent immunological cascade, and protein coronas formed on NPs can either stimulate or mitigate the immune response. Along these lines, the understanding of NP-protein corona formation in terms of physiochemical surface properties of the NPs and NP interactions with the immune system components in blood is an essential step for evaluating NP toxicity for in vivo therapeutics. This article reviews the most recent developments in NP-based protein coronas through the modification of NP surface properties and discusses the associated immune responses.</P>

Effects of carbon nanofiber on physiology of <i>Drosophila</i>

Lee, Shin-Hae,Lee, Hye-Yeon,Lee, Eun-Ji,Khang, Dongwoo,Min, Kyung-Jin Dove Medical Press 2015 INTERNATIONAL JOURNAL OF NANOMEDICINE Vol.10 No.-

<P>As nanomaterials are now widely utilized in a wide range of fields for both medical and industrial applications, concerns over their potential toxicity to human health and the environment have increased. To evaluate the toxicity of long-term exposure to carbon nanofibers (CNFs) in an in vivo system, we selected <I>Drosophila melanogaster</I> as a model organism. Oral administration of CNFs at a concentration of 1,000 μg/mL had adverse effects on fly physiology. Long-term administration of a high dose of CNFs (1,000 μg/mL) reduced larval viability based on the pupa:egg ratio, adult fly lifespan, reproductive activity, climbing activity, and survival rate in response to starvation stress. However, CNFs at a low concentration (100 μg/mL) did not show any significant deleterious effect on developmental rate or fecundity. Furthermore, long-term administration of a low dose of CNFs (100 μg/mL) increased lifespan and climbing ability, coincident with mild reactive oxygen species generation and stimulation of the antioxidant system. Taken together, our data suggest that a high dose of CNFs has obvious physiological toxicity, whereas low-dose chronic exposure to CNFs can actually have beneficial effects via stimulation of the antioxidant defense system.</P>

Destroying Deep Lung Tumor Tissue through Lung-Selective Accumulation and by Activation of Caveolin Uptake Channels Using a Specific Width of Carbon Nanodrug

Kim, Sang-Woo,Park, Jun-Young,Lee, Soyoung,Kim, Sang-Hyun,Khang, Dongwoo American Chemical Society 2018 ACS APPLIED MATERIALS & INTERFACES Vol.10 No.5

<P>The main difficulty With current anticancer nanotherapeutics comes from the low efficiency of tumor targeting. Althoughniany strategies have been investigated, including cancer-specific antibody conjugation, lung tumors remain one of the invulnerable types of cancer that must be overcome in the near future. Meanwhile, despite their advantageous physiochemical properties, carbon nanotube structures are not considered safe medical drug delivery agents, but are considered a hazardous source that may cause pulmonary toxicity. However, high-aspect-ratio (width vs. length) nanostructures can he used as very efficient drug delivery agents due to their lung tissue accumulation property. Furthermore, selection of a specific width if the carbon nanostructures can activate additional caveolin uptake channels in cancer cells, thereby maximizing internalization of the nanodrug. The present study aimed to evaluate the therapeutic potential of carbon nanotube-based nanodrugs having various widths (10-30 nm, 60-100 mn, and 125-150 nm) as a delivery agent to treat lung tumors. The results of-the present study provided evidence that both lung tissue accumulation (passive targeting) and caveolin-assisted uptake (active targeting) can simultaneously contribute to the destruction of lung tumor tissues of carbon nanotube.</P>

Improvement of Catalytic Activity of Enzymes by Masking Active Sites during Immobilization of Glucose Oxidase

MEIYU ZHANG,Chang-Joon KIM,Sung Bae KIM,DongWoo KHANG,In Young CHUNG,Dae Hwan KIM 한국생물공학회 2011 한국생물공학회 학술대회 Vol.2011 No.4

Initial Graphite Disorder of Carbon Lattice Structures Increase Surface Hydrophilicity and Protein Adsorption

Lee, Jin Woo,Park, Chul-Kyu,Yang, Dongki,Khang, Dongwoo American Scientific Publishers 2016 Journal of Nanoscience and Nanotechnology Vol.16 No.11

<P>Changes in wettability based on the dispersion properties of carbon nanotubes are generally achieved by chemical functionalization methods using acid treatments. Compared to a highly crystalline carbon structures (i.e., single-walled carbon nanotube and fullerene), low crystalline carbon structures (i.e., multi-wall carbon nanotubes and graphene) are easily functionalized in a water-based solution and exhibit excellent dispersity. However, to date, it has not been clear why low crystalline carbon structures exhibit superior dispersity relative to single-walled carbon nanotubes. In this study, we found that the initial crystallinity of the outer layers of a carbon lattice constitutes a significant material factor for determining further non-crystallization. As non-crystallized carbon lattice structures (corresponding to the D band in Raman analysis) initially increase, they can subsequently be further increased by means of ultra-sonication without any chemical treatment. Importantly, protein adsorption is more increased by reducing the surface crystallinity than a highly crystalline carbon lattice structure.</P>