Nanotoxicity Assessment toward the Applications of Carbon Nanotubes as a Small Biomolecule Carrier in Drug Delivery Systems

Carbon Nanotube (CNT) materials have superior properties in electric current carrying capacity, thermal conductivity, and thermal stability. Due to their structure with high aspect ratio, they have structural unusual toxicity and complicate safety issue in a target tissue. In optimized quantities with limited functionality, special type of CNT assembly such as “buckyball” can be used as a potential drug carrier of bioactive molecules and display with increased circulating time and acceptable functionality. We analyzed cytoxicity and inflammatory response following exposure of different size, mass, shape, and functionality of CNTs. We monitored the transport across skin, physiological perturbation of transepithelial electrical resistance (TER) during the exposure of different concentrations of CNTs. The mechanisms of CNTs’ toxicity are closely related to their structure, functional group, and surface charge on the molecule. We established the nanoscale toxicity of fullerenes of CNTs

Biological robotics and nanorobotred cells: Characterization and applications

In human body, nanorobot-like red blood cells get exposed to human body fluids and many physico-chemical changes inside while these nanorobots (fullerene structure coated hemoglobin embedded iron inorganic elements) remain safe and perform killer action against bacteria or virus. We propose this killer action as ‘nanorobot driven nanomedical treatment’ to combat a bacterial or viral infection. The red cells also act as imaging agent due to oxygen binding character. Our experiments were focused on the application of nanorobot (red cells) to make them immune resistant against viruses and making them as useful contrast agents in magnetic resonance imaging use based on their behavior in nanomagnetic fields. It consists of an injection of perhaps a few cubic centimeters of nano-sized nanorobots suspended in specific pH fluid (probably a water/saline suspension). The typical therapeutic concentration was up to 1-10 trillion (1 trillion = 10 raise to power 12) individual nanorobots, although in some cases treatment only require a few million or a few billion individual nanodevice-like red cells to be injected. Each nanorobot cell was on the order of perhaps 0.2 micron up to perhaps 0.3 microns in diameter e.g. artificial mechanical red cell floating along in the bloodstream. Nanorobots intended to travel through the bloodstream to their target will probably be 500-3000 nanometers. New technology of ‘passive diamond exteriors’ may turn out to be ideal to make immunoresistant nanorobot red cells against opsonization. Since nanorobot red cells metabolize local glucose and oxygen for energy, they are potential contrast agents for 13C-MRI, ultrasound imaging and physiological or fMRI. We believe the near possibility of travelling nanorobot carrier cells holding nanocomputer CPU working at the rate of 10 teraflops (10 raise to the power 13 floating-point operations per second) as nanomedicine robot devices. Nanorobot red cells in medical applications may be used in the form of red cells coated with diamond or diamondoid/fullerene nanocomposites in presence of inorganic elements like hydrogen, sulfur, oxygen, nitrogen, fluorine, silicon etc. for special purpose in nanoscale gears

Quantitative Analysis of the Membrane Affinity of Local Anesthetics Using a Model Cell Membrane.

Local anesthesia is a drug that penetrates the nerve cell membrane and binds to the voltage gate sodium channel, inhibiting the membrane potential and neurotransmission. It is mainly used in clinical uses to address the pain of surgical procedures in the local area. Local anesthetics (LAs), however, can be incorporated into the membrane, reducing the thermal stability of the membrane as well as altering membrane properties such as fluidity, permeability, and lipid packing order. The effects of LAs on the membrane are not yet fully understood, despite a number of previous studies. In particular, it is necessary to analyze which is the more dominant factor, the membrane affinity or the structural perturbation of the membrane. To analyze the effects of LAs on the cell membrane and compare the results with those from model membranes, morphological analysis and 50% inhibitory concentration (IC50) measurement of CCD-1064sk (fibroblast, human skin) membranes were carried out for lidocaine (LDC) and tetracaine (TTC), the most popular LAs in clinical use. Furthermore, the membrane affinity of the LAs was quantitatively analyzed using a colorimetric polydiacetylene assay, where the color shift represents their distribution in the membrane. Further, to confirm the membrane affinity and structural effects of the membranes, we performed an electrophysiological study using a model protein (gramicidin A, gA) and measured the channel lifetime of the model protein on the free-standing lipid bilayer according to the concentration of each LA. Our results show that when LAs interact with cell membranes, membrane affinity is a more dominant factor than steric or conformational effects of the membrane

Vibrational stress affects extracellular signal-regulated kinases activation and cytoskeleton structure in human keratinocytes.

As the outermost organ, the skin can be damaged following injuries such as wounds and bacterial or viral infections, and such damage should be rapidly restored to defend the body against physical, chemical, and microbial assaults. However, the wound healing process can be delayed or prolonged by health conditions, including diabetes mellitus, venous stasis disease, ischemia, and even stress. In this study, we developed a vibrational cell culture model and investigated the effects of mechanical vibrations on human keratinocytes. The HaCaT cells were exposed to vibrations at a frequency of 45 Hz with accelerations of 0.8g for 2 h per day. The applied mechanical vibration did not affect cell viability or cell proliferation. Cell migratory activity did increase following exposure to vibration, but the change was not statistically significant. The results of immunostaining (F-actin), western blot (ERK1/2), and RT-qPCR (FGF-2, PDGF-B, HB-EGF, TGF-β1, EGFR, and KGFR) analyses demonstrated that the applied vibration resulted in rearrangement of the cytoskeleton, leading to activation of ERK1/2, one of the MAPK signaling pathways, and upregulation of the gene expression levels of HB-EGF and EGFR. The results suggest that mechanical vibration may have wound healing potential and could be used as a mechanical energy-based treatment for enhancing wound healing efficiency

Multi-walled carbon nanotube-induced inflammatory response and oxidative stress in a dynamic cell growth environment

Abstract Background Rapid increase in multi-walled carbon nanotube (MWCNT) production for their industrial and biomedical applications has led to concerns over the effects of MWCNTs on human health and the environment. Both animal and in vitro studies have provided important findings about MWCNT-induced effects on the lung cells or tissues. In vitro studies have provided a considerable amount of fundamental information on MWCNT-induced effects on the specific lung cells. However, the cell culture systems used in those studies were limited by the absence of dynamic nature of lung tissues. We hypothesized that MWCNT-induced cellular responses such as proliferation, inflammation, and oxidative stress under dynamic cell growth environment may differ from those under static cell growth environment. Results In this study, we used a dynamic cell growth condition to mimic mechanically dynamic environment of the lung and characterized interleukin 8 (IL-8), reactive oxygen species (ROS), glutathione (GSH), and cell proliferation for three days following exposure of MWCNTs at different concentrations (5, 10, and 20 μg/ml) to A549 cell monolayer under both static and dynamic cell growth conditions. Our results demonstrated the distinct differences in the levels of inflammatory response and oxidative stress between static and dynamic cell growth conditions. Conclusions In conclusion, the dynamic cell growth system used in this study provided important changes in cellular responses that were not found in the static cell growth system and were similar to animal studies. The dynamic cell growth system can be considered as a viable alternative to in vivo test system in combination with existing in vitro static cell growth systems to evaluate the effect of MWCNTs on cellular responses in the respiratory system.</p

Antimicrobial effect of silver-impregnated cellulose: potential for antimicrobial therapy

Abstract Background Silver has long been known to have antimicrobial activity. To incorporate this property into multiple applications, a silver-impregnated cellulose (SIC) with low cytotoxicity to human cells was developed. SIC differs from other silver treatment methods in that the leaching of silver particles is non-existent and the release of ionic silver is highly controlled. Results Candida albicans, Micrococcus luteu, Pseudomonas putida, and Escherichia coli were used for antimicrobial testing. No microbial cells were able to grow in the presence of SIC at concentrations above 0.0035 Ag w/v %. Even at a concentration of 0.00035 Ag w/v %, P. putida and M. luteu failed to grow, and C. albicans and E. coli exhibited diminished growth. To determine the cytotoxic effect of silver on human cells, five different concentrations of SIC were tested on human fibroblasts. In SIC concentrations of 0.035 Ag w/v % and below, no cytotoxicity was observed. Conclusion The optimal concentration of SIC for a broad range of anti-microbial activity and low or negligible cytotoxicity was 0.0035 Ag w/v %. Although the highly controlled releasing characteristics of SIC would prove a substantial improvement over current technologies, further investigation for genotoxicity and other biocompatibility test will be required.</p