5 simple tips to prevent jaundice _ nanomedicine

Indian scientists working on nano medicine treatment for jaundice

The age-old home remedy for jaundice - nimbu paani or lemon juice – has now got a 21st century spin, thanks to Indian scientists. They have literally squeezed lemons to nano-dimensions to create a nanodrug for speedy and accurate therapy of the disease. Here are 5 simple tips to prevent jaundice.

Widening the scope of nanomedicines in India, scientists in West Bengal have designed special nanoparticles that break down bilirubin – the yellow pigment found in bile, a fluid made by the liver. Essential to liver health, higher than normal levels of bilirubin in blood (hyperbilirubinemia), may indicate certain diseases, including jaundice, in adults as well as newborns. Now, a smartphone app that detects jaundice in babies.

High levels may lead to brain damage or even death in newborns and adults, if not treated. To combat this, we designed manganese oxide nanoparticles capped with citrate, a derivative of citric acid found in citrus fruits such as lemons,’ Nabarun Polley, of S. N. Bose National Centre for Basic Sciences, Kolkata, told IANS. Polley, a senior researcher at the Centre’s department of chemical, biological and macro-molecular sciences, explained that this nano-hybrid helps to degrade bilirubin and bring it down to a normal level swiftly. ‘It is actually like nimbu paani administered through nanoparticles,’ said Polley, adding lemon juice is usually suggested due to its cleansing nature. Use these home remedies to relieve the symptoms of jaundice or hepatitis.

Through experiments performed on lab mice, Polley and his co-investigators at Jadavpur University and Dey’s Medical, showed the nanoparticles to be safe, compatible with the body, and proved that they had the ability to act directly and specifically on the target-bilirubin.This ensures the nanodrug doesn’t affect any organ. There were no toxic effects after the particles were injected into the mice and parameters like blood cell count didn’t change,’ said collaborator Soumendra Darbar, research and development division, Dey’s Medical Stores (Mfg.) Ltd. Read: 8 jaundice symptoms you need to watch out for.

In fact, this precision which is the product’s USP, also takes care of the time factor. ‘It brought down high bilirubin levels within two hours (in mice) while the commercially available drug silymarin took more than a day to control the levels for the equivalent dose,’ said Polley, adding the group has been working on this specific nanoparticle for the last five years.

The latest findings, which are currently in press for publication in the Nanomedicine journal, open a new door for ‘cost-effective and efficient therapeutic treatment of hyperbilirubinemia, jaundice and associated diseases,’ according to group leader Samir Kumar Pal. ‘We have been working on detection as well as the treatment aspect of elevated bilirubin. In the near future, we could help avoid preventable deaths of newborns,’ said Pal, professor at the Centre’s department of chemical, biological and macro-molecular sciences. 

Union Minister of Science and Technology Harsh Vardhan, post his visit to Pal’s lab recently, had highlighted on Facebook that neonatal jaundice deaths, comprise 18 percent of newborn mortality in India. He was particularly impressed with a non-invasive, computer-based fibre-optic detector fabricated by the group that detects bilirubin levels within three seconds by shining light on the white part of one’s eye.

‘Nanomedicine has huge potential for India as it has elsewhere in the world. Specially, diagnostics promises to offer cheap and faster way for detecting diseases for India. This has a huge potential for India because our healthcare is not as widespread,’ said Praveer Asthana, Mission Director, Nano Mission,Department of Science & Technology, India.

Source: IANS

http://www.thehealthsite.com/news/indian-scientists-working-on-nano-medicine-treatment-for-jaundice/

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carbon nanotube

Particle Characterization and Centrifugation Tools from Beckman Coulter for Nanomedicine Applications

Carbon Nanotube Preparation

Single-walled carbon nanotubes (Sigma-Aldrich) and 0.2% 1, 2-distearoyl-phosphatidylethanolamine -methyl-polyethyleneglycol (DSPE-mPEG, 5 kDa molecular weight, Laysan Bio) were mixed in 10mL of water. Well-dispersed carbon nanotubes were created by bath sonicating the solution for 30 minutes, as per previously established procedures.  

5 mL of SWCNT was centrifuged  in open-top polycarbonate centrifuge tubes (Beckman Coulter P/N 343778) at 22°C, 55,000 RPM (~I31,000 x g) for two minutes using a TLA-120.2 rotor in an Optima MAX-XP Ultracentrifuge. The top 650µL of supernatant was collected carefully to avoid disrupting the pelleted aggregates.

Using 10 kDa, Amicon Ultra 0.5 mL Centrifugal Filters (Millipore) with a Beckman Coulter Microfuge 20 microcentrifuge, concentration of the ultracentrifuged SWCNT(UCF’d SWCNT) and the uncentrifuged SWCNTs (As made SWCNT) was performed.

Measurement of the concentration was carried out using a UV-Vis-NIR spectrophotometer (Paradigm, Molecular Devices) and the established mass extinction coefficient of SWCNTs at 808nm of 46.5L/g*cm2 Deionized water was used to dilute the concentrated  UCF'd SWCNTs and As-Made SWCNTs to 0.6mg/mL, 0.3mg/mL, and 0.06mg/mL concentrations.

Toxicity Assay

24 hours prior to adding nanotubes, MCF-7 breast cancer cells were plated at a density of 0.08 x 106 per well in a 24-well plate with 900µL of RPMI/10% FBS (Invitrogen). Using one of the wells before nanotubes were added, cell growth and viability were confirmed. On the next day, 100µL of SWCNT samples were added to the wells.

In total, there were six SWCNT groups (n=2/group):

• 0.06 mg/mL UCF'd SWCNTs
• 0.06 mg/mL As-Made SWCNTs
• 0.03 mg/mL UCF'd SWCNTs
• 0.03 mg/mL As-Made SWCNTs
• 0.006 mg/mL UCF'd SWCNTs
• and 0.006 mg/mL As-Made SWCNTs.

To provide a control, 100µL of DSPE-mPEG only sample was added to the wells.  

In total, there were three surfactant buffer control groups (n=2/group):

• 0.2 mg/mL DSPE-mPEG;
• 0.02 mg/mL DSPE-mPEG;
• 0.002 mg/mL DSPE-mPEG.

Lastly, control 1 (n=1) was a complete control, with cells left untouched and 100µl of sterilized water was added to control 2(n=1). After 24 hours, in order to enable counting in the Vi-CELL XR, all wells were rinsed using PBS and then trypsinized and mixed in 1mL of PBS. To minimize aggregated nanotubes being counted as cells a novel cell type was developed using the Vi-CELL XR software. Comparison of cell viability and difference in the two solutions was carried out using the percentages of viable cells.

Figure 2. Cell Imaging. MCF-7 cells were imaged under an optical microscope after 24 hours of incubation with SWCNT. The cells, incubated with either 0.06 mg/mL As-Made SWNT (left image) or 0.06 mg/mL ultracentrifuged SWNT (right image), have not yet reached confluence. Black aggregates of SWNT can be seen in the image on the left; these aggregates are difficult to wash away without washing away the cells as well. The aggregates have absorption and fluorescence properties that will skew traditional toxicity assays.

Figure 3. Viability Results. At all concentrations, ultracentrifuged SWCNT (designated by UC) had minimal toxicity; 75% or more of the MCF-7 cells remained viable 24 hours after incubation. Contrastingly, SWCNT that were not centrifuged and contained aggregated species (designated by AG) had increasing toxicity toward MCF-7 cells that scaled with increasing concentration. At a stock concentration of 0.6 mg/mL, corresponding to a concentration in solution with cells at 0.06 mg/mL, the aggregated SWCNTs had greater than 50% cell death.

Results and Discussion

One of the key challenges of nano-biomedicine is aggregated nanoparticles. This article examined the  toxicity of As-Made SWCNTs (which included visible aggregates); however, this information is representative of most nanoparticles. The SWCNTs were separated into the As-Made group and the ultracentrifuged group. The former group did not undergo any purification for aggregate removal while the latter underwent ultracentrifugation in the Beckman Coulter Optima MAX-XP ultracentrifuge.

Although centrifugation is effective for the removal of aggregated nanoparticles, the research workflow is somewhat hindered by long centrifugation times, of at least 6 h at low speeds (5,000 x g to 22,000 x g). This new ultracentrifugation technique shows that a high-speed, two-minute ultracentrifugation can achieve the same biocompatibility and individual solubilized SWCNTs as the longer centrifugation time can, offering researchers a 180-fold time saving.

Dynamic light scattering data and optical images captured with the DelsaMax PRO provide proof that all aggregated SWCNT has been eliminated using the rapid ultracentrifugation. It was possible to collect the toxicity data in this study because  Vi-CELL XR was used; aggregates have a strong absorption that would confound typical MMP and MTT toxicity assays.

The Vi-CELL XR was programmed to specifically look for spherical cells having defined outlines in a sharply delineated size range, to minimize the counting  of carbon nanotube aggregates as either dead or viable. Due to the large number of aggregates present even after cell washing, the  Vi-CELL XR optimization is very important.

Ultracentrifuged nanotubes were run without any cells, as a control, and in this trial, the  Vi-CELL XR did not count a single cell as dead or live.

Figure 4. Size Distribution Data. Single-walled carbon nanotubes, after sonication in surfactant, still have a number of aggregated species. Size distribution, determined by Dynamic Light Scattering on the DelsaMax PRO, showed two broad species (red line). The first size range, roughly 100 nm in diameter, represents individually solubilized carbon nanotubes. The second species, containing mostly aggregated carbon nanotubes, has a diameter peak closer to one micron in size. After a two-minute ultracentrifugation, the SWNT demonstrate only a single broad species at 100 nm, indicating that virtually all aggregates have been removed. This is further indicated by a 59% decrease in polydispersity. Interestingly, the zeta potential remains unchanged between aggregated and centrifuged carbon nanotubes. This is most likely due to the fact that steric repulsion, from the Poly(ethylene glycol) surfactant, provides most of the stability to the carbon nanotubes, while electrostatic repulsion does not play a major role.

Figure 5. Flowchart

Conclusions

Compared with  ultracentrifuged SWCNT, aggregates show higher toxicity, something that can be attributed to poor surfactant coverage and the larger size of aggregated SWCNT. The surfactant-free surface is more exposed in aggregated SWCNT and this increased surface availability of SWCNT contributes directly to increasing the reactive oxygen species (ROS). Also, on the whole, As-Made or aggregated SWCNTs are much larger, as shown by the dynamic light scattering data. The larger size of  SWCNT can block cell-signaling pathways or hinder cellular action and thereby inhibit cell growth. It is therefore essential that removal of aggregated nanoparticles is performed before being used in vitro or in vivo.

References

1. Liu Z et al; Carbon materials for drug delivery & cancer therapy—Materials Today. 14.7; 316-323: (2011).
2. Hong G et al; In Vivo Fluorescence Imaging with Ag2S Quantum Dots in the Second Near-Infrared Region—Angewandte Chemie. 124.39; 9956-9959: (2012).
3. Levina L et al; Efficient Infrared-Emitting PbS Quantum Dots Grown on DNA and Stable in Aqueous Solution and Blood Plasma—Advanced Materials. 17.15; 1854-1857: (2005).
4. Welsher K, Sherlock S P and Dai H; Deep-tissue anatomical imaging of mice using carbon nanotube fluorophores in the second near-infrared window—Proceedings of the National Academy of Sciences. 108.22; 8943-8948: (2011).
5. Smith A M, Mancini M C, and Nie S; Second window for in vivo imaging—Nature Nanotechnology. 4.11; 710: (2009).
6. Zavaleta C et al; Noninvasive Raman spectroscopy in living mice for evaluation of tumor targeting with carbon nanotubes—Nano letters. 8.9; 2800-2805: (2008).
7. Davoren M et al; In vitro toxicity evaluation of single-walled carbon nanotubes on human A549 lung cells—Toxicology in vitro: an international journal published in association with BIBRA. 21.3; 438: (2007).
8. Wörle-Knirsch J M, Pulskamp K and Krug H F; Oops they did it again! Carbon nanotubes hoax scientists in viability assays—Nano letters. 6.6; 1261-1268: (2006).
9. Ren H et al; Toxicity of single-walled carbon nanotube: How we were wrong -Materials Today. 13.1: 6-8: (2010).
10. Wick P et al; The degree and kind of agglomeration affect carbon nanotube cytotoxicity—Toxicology letters. 168.2; 121-131: (2007).
11. Lewinski N, Colvin V and Drezek R; Cytotoxicity of nanoparticles—Small. 4.1; 26-49: (2008).
12. Robinson J T et al; High performance in vivo near-IR (> 1 μm) imaging and photothermal cancer therapy with carbon nanotubes—Nano Research. 3.11; 779-793: (2010).
13. Donkor A D et al; Carbon nanotubes inhibit the hemolytic activity of the pore-forming toxin pyolysin—Nano Research. 2.7; 517-525: (2009).
14. Kam N W S et al; Carbon nanotubes as multifunctional biological transporters and near-infrared agents for selective cancer cell destruction— Proceedings of the National Academy of Sciences. 102.33; 11600-11605: (2005).
15. Robinson J T et al; In Vivo Fluorescence Imaging in the Second Near-Infrared Window with Long Circulating Carbon Nanotubes Capable of Ultrahigh Tumor Uptake—Journal of the American Chemical Society. 134.25; 10664-10669: (2012).
16. Ghafari P; Impact of single-walled carbon nanotubes on ciliated protozoa & bacteria - Master’s Thesis University of Waterloo: (2009).
17. Grabinski C et al; Effect of particle dimension on biocompatibility of carbon nanomaterials - Carbon. 45.14; 2828-2835: (2007).

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source : http://www.news-medical.net/whitepaper/20150519/Particle-Characterization-and-Centrifugation-Tools-from-Beckman-Coulter-for-Nanomedicine-Applications.aspx

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kill cancer cells

World first as scientists use cold sore virus to attack cancer cells

Scientists have the first proof that a “brand new” way of combating cancer, using genetically modified viruses to attack tumour cells, can benefit patients, paving the way for a “wave” of new potential treatments over the next decade.

Specialists at the NHS Royal Marsden Hospital and the Institute of Cancer Research (ICR) confirmed that melanoma skin cancer patients treated with a modified herpes virus (the virus that causes cold sores) had improved survival – a world first.

In some patients, the improvements were striking. Although all had aggressive, inoperable malignant melanoma, those treated with the virus therapy – known as T-VEC – at an earlier stage survived on average 20 months longer than patients given an alternative.

In other patients results were more modest, but the study represents a landmark: it is the first, large, randomised trial of a so-called oncolytic virus to show success.

source :  http://www.independent.co.uk/life-style/health-and-families/health-news/world-first-as-scientists-provide-proof-that-viruses-can-combat-cancer-10277315.html?utm_source=dlvr.it&utm_medium=twitter

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NANOTECHNOLOGY

Blood to feeling: Scientists turn adult human blood cells into neurons

Stem cell scientists can now directly convert adult human blood cells to both central nervous system (brain and spinal cord) neurons as well as neurons in the peripheral nervous system (rest of the body) that are responsible for pain, temperature and itch perception. This means that how a person's nervous system cells react and respond to stimuli, can be determined from his blood.

Source: McMaster University

SPECIAL THANKS

Antonei B Csoka, PhD

Assistant Professor, 

Dept. of Anatomy,

 Howard University

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cancer cells

Cell Division and Cancer

Cancer cells are cells gone wrong — in other words, they no longer respond to many of the signals that control cellular growth and death. Cancer cells originate within tissues and, as they grow and divide, they diverge ever further from normalcy. Over time, these cells become increasingly resistant to the controls that maintain normal tissue — and as a result, they divide more rapidly than their progenitors and become less dependent on signals from other cells. Cancer cells even evade programmed cell death, despite the fact that their multiple abnormalities would normally make them prime targets for apoptosis. In the late stages of cancer, cells break through normal tissue boundaries and metastasize (spread) to new sites in the body.

How Do Cancer Cells Differ from Normal Cells?

In normal cells, hundreds of genes intricately control the process of cell division. Normal growth requires a balance between the activity of those genes that promote cell proliferation and those that suppress it. It also relies on the activities of genes that signal when damaged cells should undergo apoptosis.

Cells become cancerous after mutations accumulate in the various genes that control cell proliferation. According to research findings from the Cancer Genome Project, most cancer cells possess 60 or more mutations. The challenge for medical researchers is to identify which of these mutations are responsible for particular kinds of cancer. This process is akin to searching for the proverbial needle in a haystack, because many of the mutations present in these cells have little to nothing to do with cancer growth.

Different kinds of cancers have different mutational signatures. However, scientific comparison of multiple tumor types has revealed that certain genes are mutated in cancer cells more often than others. For instance, growth-promoting genes, such as the gene for the signaling protein Ras, are among those most commonly mutated in cancer cells, becoming super-active and producing cells that are too strongly stimulated by growth receptors. Some chemotherapy drugs work to counteract these mutations by blocking the action of growth-signaling proteins. The breast cancer drug Herceptin, for example, blocks overactive receptor tyrosine kinases (RTKs), and the drug Gleevec blocks a mutant signaling kinase associated with chronic myelogenous leukemia.

Other cancer-related mutations inactivate the genes that suppress cell proliferation or those that signal the need for apoptosis. These genes, known as tumor suppressor genes, normally function like brakes on proliferation, and both copies within a cell must be mutated in order for uncontrolled division to occur. For example, many cancer cells carry two mutant copies of the gene that codes for p53, a multifunctional protein that normally senses DNA damage and acts as a transcription factor for checkpoint control genes.

nano medicine

DEVELOPMENT @ NANO MEDICINE

Nano medicine has been developing rapidly in recent years, particularly in the development of novel nano tools for medical diagnosis and treatment. For instance, a new trend is becoming prevalent in developing nano systems for simultaneous tumor diagnosis and therapy.

This requires high versatility of the nano carriers with multiple functionalities of cell targeting, drug storage, optical imaging, and effective means of treatment such as magnetic and photo thermal hypothermia, photo dynamic therapy, and drug release via various intelligent mechanisms (pH, temperature, and biochemical variations in the tumor environment).

A new terminology "thermostatic" has been frequently used and applied in pre-clinical research and trials. A nano system can simultaneously achieve both cell targeted in vivo imaging and photothermal treatment of cancer. While achieving concurrent high spatial and temporal resolution of the lesions via cell targeting; special non-evasive treatments are implemented at the same time by various means, such as localized drug release, hypothermia, and photo-thermal therapy.

Inspired by these challenging problems in biomedical fields, the development of the nanotechnologies will be the key in addressing some of the critical issues in medicine, especially in early cancer diagnosis and treatment.

In this book published by World Scientific, Bio-inspired Nanomaterials and Devices summarizes the most recent developments in nanomaterials, biotechnology, and medical diagnosis and therapy in a comprehensive fashion for researchers from diverse fields of chemistry, materials science, physics, engineering, biology, and medicine. Not only does the book touch up on the most fundamental topics of nanoscience, but also deal with critical clinical issues of transitional medicine.

The book is written in a straightforward and tutorial fashion, typically suitable for technical non-specialists. All chapters are written by active researchers in frontier research of nanobiomedicine. This book will provide timely and useful information for the progress of nanomaterials and biomedical applications.

nano medicine

Nanomedicine is the medical application of nanotechnology. Nanomedicine ranges from the medical applications ofnanomaterials, to nanoelectronic biosensors, and even possible future applications of molecular nanotechnology. Current problems for nanomedicine involve understanding the issues related to toxicity and environmental impact ofnanoscale materials (materials whose structure is on the scale of nanometers