I wish you all happy and prosperous new year

Hoping to come up with great research updates in Nanotechnology to all

in this New Year 2014

Cancer Immunotherapy - Breakthrough of the year

"This year marks a turning point in cancer, as long-sought efforts to unleash the immune system against tumors are paying off - even if the future remains a question mark" stated by Jennifer Couzin-Frankel in the article published in Science on 20th December, 2013. With the ending of this year the Science magazine has surveyed the outstanding works done in the whole year. Out of many speculations and expectations, the panel chose Cancer Immunotherapy as the breakthrough of this year. Is it really worth to mention as breakthrough? Let’s see.

"Cancer", one word that kill the patient psychologically than the actual unwanted mass of cells in his/her body. The patients have in mind that day by day they are reaching to the end of their life. May be this can be avoided in the developed countries but it is prevalent in developing and underdeveloped countries. Novel therapeutic ways, targeting sites, therapeutic materials are being explored from a long time by researchers around the world with the millions of dollars as funding from the governments. Still for the researchers’ the disease is a mystery.

The panel has found some light in this deep dark unsolved puzzle for decades or say centuries! So, the breakthrough of this year "Cancer Immunotherapy" is the new field where the immune system is treated to kill cancer cells. Up to now the cancer cells are treated directly without affecting the immune system. This is a strategy where, say, ‘x’ is treated to kill y.  ‘x’ will signal a cascade of changes that result in the killing of ‘y’ rather than directly giving a molecule to kill ‘y’. Though this kind of treatment strategy is new, it is working. In this article, published in science, the author pointed some potential antibodies that target different sites on the T-Cells. They are Cytotoxic T-lymphocyte antigen 4 (CTLA-4), Programmed death 1 (PD 1) and Chimeric antigen receptor (CAR) therapy. 

The pink color antibodies are binding to the blue color receptors

signalling a cascade of events killing the cancer cells

(J Couzin-Frankel Science 2013;342:1432-1433)

Courtesy: Science magazine (AAAS)

The basic working principle of all these therapies is to target the T-cells with the antibodies to specific receptor marker on the T-cells. These antibodies block the targeted receptors and then signal a cascade of events that result in the killing of cancer cells. The clinical trials done on these strategic treatment modalities showed successful development in the patient’s survival rate and decrease in the tumor size. The recurrence of the disease is also decreased significantly. The peculiarity of these treatment modalities is that they can be used in any kind of tumors either benign or metastasis without potential side effects. The researchers are trying to decipher the mechanism of activity, the role of various molecules in killing the cancer cells.

Hoping for a cancer free society, the Cancer Immunotherapy, breakthrough of the year (agreeing worth to mention as breakthrough) should be materialized and also available to millions of cancer patients around the world. 

I wish you all Happy New Year.

Layer by Layer nanocarriers for Drug Delivery

     The Erlich's "Silver Bullet" is the final goal for any drug delivery researcher to accomplish. The development of various engineered nanocarrier systems for the delivery of drugs to the specific diseased locations in the body possess fresh challenges every time. The stability of the nanocarrier is very important inside the body. The carrier when injected into the blood stream it should not be degraded or dissolved immediately. At the same time it should not elicit any immune response. Most importantly, the carrier should not leak the drug until it reach the target site. To attain these basic but important things, researchers mostly chose the systems that have the stable charge distributed all over the carrier system. Research showed that the positive charged systems elicit immune response at a faster rate compared to negative and neural charged carriers.

     While designing a carrier for a particular drug the architecture of the carrier are very important. The shape and nature of the carrier plays an important role. Spherical carrier of different chemical nature like polymers, liposomes, nanoparticles are widely exploited. The polymer drug carriers are mainly used in the cases where the drug has to be released for a long time. For the case of liposomes, it is burst release or quick release and their life time at the targeted site is less. These carrier choices, to achieve specific duties, helps in enhancing the effectiveness of the carrier and also decrease the number of drug dosage times for the patient.

     Though these carriers seems to be promising, still there is room to increase their efficiency of drug loading and drug targeting particularly DNA or si-RNA targeting. The polymers such as Poly-L-Lysine, Polyethyleneimine etc are widely used to deliver these genetic material. These polymers are positive charged polymers that form tight complexes with the negatively charged DNA or si-RNA. A more protection is needed for this genetic material from the surrounding molecules and enzymes that degrade these once injected into the blood stream. A new approach of designing the delivery carriers to overcome these problems is reported recently. The layer-by-layer approach for the delivery of genetic material is reported by Deng et al.,  published in ACS Nano. 

                                                                         The cartoon showing the Layer-by-Layer designed drug delivery carrier system

Such engineered carrier systems are the future for a sustained, stable and effective delivery of the load to the targeted site.

Reference:

Zhou J. Deng, Stephen W. Morton, Elana Ben-Akiva, Erik C. Dreaden, Kevin E. Shopsowitz, Paula T. Hammond†, Layer-by-Layer Nanoparticles for Systemic Codelivery of an Anticancer Drug and siRNA for Potential Triple-Negative Breast Cancer Treatment. ACS Nano 7 (2013) 9571-9584.

Sensitive detection of circulating tumor cells

Cirulating tumor cells are the prime things that detach from the solid tumor and reach the other parts of the body such as lungs, liver, spleen etc. Such a cancer state is called Metastasis which is an advanced state of the cancer. Some cancers like pancreatic cancer develop symptoms at this late stage. Hence the treatment is difficult and the patient survival rate is very low while the mortality rate is 85% (According to American cancer society statistics, 2013).

There is a clear need for the identification of these cells in the blood circulation so that the initiation of treatment methods to the patients will be easy for physicians. Currently we have several microfluidic based detection systems where these microfluidic chips will collect the cells and filter them. These cells will be cultured and identified. It is a very long and time consuming process. For a better detection system for identifying these circulating tumor cells, the device should be simple, sensitive and cost effective.

The recent paper published in Nature nanotechnology on 29 september 2013 developed a sensitive detection method to identify these circulating tumor cells. The authors/researchers from University of Michigan used the graphene oxide as the detection material for detecting the circulating tumor cells. The paper is very interesting and it mentioned the sensitivity of the fabricated device in detecting the circulating tumor cells such as PC-3, pancreatic cancer cells, MCF-7 and HS578T breast cancer cells.

The complete article will be obtained from  

http://www.nature.com/nnano/journal/v8/n10/abs/nnano.2013.194.html

Microparticles for brain drug delivery

The usage of nanoparticles for the therapeutic applications is in research for quite a long time. The fruits of the research are come out now. The clinical trails for various drug delivery formulations are in progress. The recent studies of the nanoformulations are well discussed in this article. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3260950/


Eventhough we have many liposome formulations, the commercialization of polymer nanodrug formulations hasn't seen light yet. The recent study of pennstate university research group has showed the sustained release of the microparticles for brain drug delivery. The blood brain barrier is the primary limitation step for any drug to enter into brain. The liposomes are widely used for brain drug delivery as they are having the lipid component which can easily enter into the brain than other formulations. But the draw back of liposomes is the burst release of the drug. Most of the drug will be released within the short period of time. This causes the patient has to take more doses at regular periods of time.The pennstate research group led by Dr. Mohammad Reza Abidian, assistant professor of bioengineering, chemical engineering and materials science and engineering has mentioned that "Brain tumors are one of the world's deadliest diseases," which needs to be addressed with a potential carrier system. Their work has been recently reported in Science daily. In their words. "We are trying to develop a new method of drug delivery," said Abidian. "Not intravenous delivery, but localized directly into the tumor site."
Current treatment already includes leaving wafers infused with the anti-tumor agent BCNU in the brain after surgery, but when the drugs in these wafers run out, repeating invasive placement is not generally recommended.
"BCNU has a half life in the body of 15 minutes," said Abidian. "The drug needs protection because of the short half life. Encapsulation inside biodegradable polymers can solve that problem."

The research groups around the world are trying to have a suitable carrier system that can cure the brain cancer. The work done by pennstate university is one of the good work in a new approach. Hope new thinking in new ways provide the solution to the long suffering problem.

Courtesy: www.sciencedaily.com

Magnetic nanoparticles in Gene therapy

          The transfection of the suitable genes into cells is the primary target of gene therapy. Earlier the genes are trasfected by binding with gold nanoparticles and injecting by a transfection gun. Later the electroporation technique is used where the small electric voltage is applied which increases the permeability of the cell  which leads to intake of more genes of interest. Recently, the use of magnetic nanoparticles is rapid in studying the gene delivery mechanism for various diseases and various kinds of genes of interest. The delivery of genes has to overcome the barriers of the skin if it is transfected externally or if to the brain it has to cross the blood-brain barrier (BBB) a key rate limiting step in the drug/gene delivery to brain. People employ mostly liposomes for brain drug delivery as they easily pass the BBB. Several researchers are trying to get the correct carrier with proper mechanism to have a successful gene transfection. Companies like Nano Therics (www.nanotherics.com) are provinding various instruments for gene transfection by magnetic nanoparticles. 

          For the recent news on gene delivery using magnetic nanoparticles, the readers are directed to the following link http://www.sciencedaily.com/releases/2013/05/130530111153.htm. Eventhough the research progresses, still there is much to go. 

Toxicological aspects of nanoparticles

Mr. Smith, stock broker for a famous firm, has interest in technology. So he always update his home electrical appliances and other gadgets regularly as there are no money constraints for him. Recently he purchased a new silver nanotechnology based washing machine. The sales person describe nanotechnology is the current highest technology which keeps the clothes away from bacteria and bad odour. A sales person knowing that much is good. He insisted on the beneficial part of nanoparticles and nanotechnology. Does he forget the other face of nanomaterials?! The toxic nature of nanoparticles, unfortunately, has become a major concern for environmentalists rather than general public. 

Do nanoparticles are toxic? Yes, nanoparticles are toxic but with high dosage concentrations. The study of nanoparticle toxicology is being carried out in many labs around the world and also publishing the results in many journals of various big publishers. The scientific community is concerned over the toxicity of the nanoparticles more than the policy makers and public. Nanoparticles are the smallest particles of metal or non metal or oxides etc., which are of the order thousand time lesser than micron size. Such small nanoparticles can reach to very end of the lungs, if inhaled, and very end of the blood vessels in the tissue if entered. Such a kind of particles are generally threat to the human body but thanks to god for giving such a strong immune system mechanism and defence processes, that the particles can be eliminated by RES system mostly, Urination etc. The problem comes when the dosage is high.

The high dosage of nanoparticles is toxic to cells which are the fundamental units of human body. The malfunction of a cell division leads to the generation of a bunch of immortal cells called as tumor and famous with the name "Cancer". Upto now we are talking about the toxicity of nanoparticles to healthy cells by dose dependent manner. Can't we use this aspect for the killling of cancer cells! A recent report in Nano Today authored by Stefan J. Soenen [1] reviewed the same aspect elaborately. The cancer cells are more prone to nanoparticle toxicity than the healthy cells which is an advantage to fight against cancer. The fluidity of the cancer cells enables the easy intake of nanoparticles which can act by two mechanisms. One way is to elicit the apoptosis pathway and the other one is the long term metal leaching. In the first mechanism, the nanoparticles are receptor mediated uptaken or by endocytosis stays for a long time inside the endosomes. The degeneration of the nanoparticles cause  pH changes in endosomes which then give signals to the nucleus to self destruct which is nothing but apoptosis. The other mechanism is the long term staying of the particle inside the cell and releasing the metal ions for a longer periods. These metal ions will be toxic to cells. It was proved that the metal ions alone given to cells are not affected than the cells given metal nanoparticles. The scientific understanding of the behaviour of nanoparticles toxicity to cells help in understanding the dose concentration and also the nanoparticle properties.

Toxicity studies of nanoparticles play a crucial role in understanding the demon of high dosage nanoparticles which can also become an angel in killing cancer cells. The two faces of nanoparticles is beneficial as per their application. The vibrant future of nanotechnology in providing the beneficial and commercial products is ahead.

[1]Stefaan J. Soenen, Jo Demeester, Stefaan C. De Smedt, Kevin Braeckmans. Turning a frown upside down: Exploiting nanoparticle toxicity for anticancer therapy.Nano Today (2013) 8, 121—125.

Drug delivery in Cancer

Cancer is an unanswerable question for researchers around the world from many decades. Exploring wide areas of biology, medicine and interdisciplinary fields like nanotechnology is going on to find a suitable molecule to kill cancer. The prescription of drugs (chemotherapy) to cancer patients by physicians across the globe after tumor removal is the current treatment modality. So the drugs play an important role in the treatment of cancer. The effectiveness of the drugs is limited while the side effects are more. But patients, as there is no other go, are ready to take these drugs.

From the last decade, the advent of nanotechnology in the delivery of medicine has paved the way for a new field called “Drug Delivery”. The main objective of this field is to develop various nanoformulation (a drug loaded nanocarrier) that is targeted to the specific diseased site, stay for a longer time in the body and minimizing side effects. Not every nanoformulation will fulfill all these three, but most of them will.

A recent development from Mc Neil’s Lab, part of the federally funded research and development center operated by SAIC-Frederick for the National Cancer Institute, worked with a drug company to reformulate TNF-alpha by coupling it with gold nanoparticles. Using the nanotechnology-enhanced protein, it appears possible to safely inject up to three times the amount that had been lethal with previous versions. The modified drug has been through a Phase 1 clinical trial and is entering Phase 2[1].

In future we can expect much more will come from many labs around the world and hope for a cancer free society.

[1] courtesy from Science daily, New Delivery for Cancer Drugs,May 7, 2013.

The Power of Magnetic Nanoparticles as Detection Agents of Single Bacteria

 Nanotechnology based detection assays are not new within the last decade. A variety of unique strategies are being tried by various researchers around the world to identify the pathogenic bacteria using magnetic nanoparticles. 

 A recent paper published in nature nanotechnology reports the detection of a single pathogenic bacteria using DNA sandwich hybridization technique where the target DNA (analyte) is being sandwiched by the DNA attached to the magnetic nanoparticles. Here, the corresponding author Ralph Weissleder, a pioneer scientist and doctor, used polymeric nanoparticle conjugated with magnetic nanoparticles as magnetic beads which hosted the complementary DNA sequences to the target bacterial 16S ribosomal sRNA. The micro NMR is being used as the detection system. The micro NMR is the actual NMR which is fabricated to the micron size holds a sample of ~ 2 micro liters. The detection sensitivity of the bacterial RNA sequences were checked and validated over 13 pathogenic bacterial species. They claim that the system is robust in detection of pathogenic bacteria with high sensitivity. Besides, the same approach can be used to identify the unknown bacteria by employing the target specific primers attached to the magnetic beads. This is a dual approach for a single nanopaticle system.

The pros of this work are that they developed and validated an RT-PCR based bacterial detection assay with low sensitivity and high specificity.

The cons of this work are the cost issues where the procuring of the primer sequences and RT-PCR with all the enzymes are costly will be a non possible one except in very high infrastructure hospitals or clinics.

The article was studied from http://www.nature.com/nnano/journal/v8/n5/pdf/nnano.2013.70.pdf

The image was made using Inkscape 0.48 version software