Nanocarrier has improved the drug action in pancreatic cancer

Hi all. As I told in my previous blog, this is the second post regarding my work that recently published. Pancreatic cancer is the most aggressive of all cancers. The five year survival rate of a patient is less than 6 %. Out of 100 persons diagnosed with pancreatic cancer 85 persons are mortal. For treating of such an aggressive disease "Gemcitabine" is recommended as the standard chemotherapy with 1000 mg/meter square. The poor bio-availability of the drug inside tumor environment and rapid efflux mechanisms of pancreatic cancer cells are the prime reasons for the pancreatic cancer resistance towards gemcitabine. To over come this drawback, a nanocarrier that is biocompatible and biodegradable with sustained drug release shall be effective in treating pancreatic cancer.

Cartoon depicting the Gemcitabine (Green) loaded PLGA (grey) nanospheres

Our work, published in Materials Science and Engineering: Chemistry, discussed about gemcitabine loaded poly(Lactide-co-glycolide) (PLGA) nanospheres as an effective treatment modality for pancreatic cancer. We have encapsulated the drug into PLGA nanospheres by water-oil-water emulsion method and achieved 15 % of encapsulation which is higher compared to existing literature, as it is tough to load a hydrophilic drug into a hydrophobic polymer. The gemcitabine was proved in the literature to be present in the polymer chain foldings and crevices formed by polymer chains inside the PLGA nanospheres. The drug loaded gemcitabine PLGA nanospheres provided a sustained drug release for 41 days. The nanospheres showed the bulk erosion degradation which enhances the release of drug in a sustained manner. The nanospheres were taken into cells by non-energy dependent mechanism. The specific targeting using an antibody will facilitate specific cancer cell attack by the nanocarrier.

Overall the biodegradable and biocompatible PLGA with gemcitabine loaded inside shall be a promising nanocarrier for pancreatic cancer treatment.

Reference

L.R.Jaidev, Uma Maheswari Krishnan, Swaminathan Sethuraman, (2015)  Gemcitabine loaded biodegradable PLGA nanospheres for in vitro pancreatic cancer therapy Material Science and Engineering:C , 47, 40–47.

http://www.sciencedirect.com/science/article/pii/S0928493114007280 

Nanomotors - Cancer Killers

The vision of the Eric Drexler in his famous book “Engines of creation” discusses the possible ways of developing the nanorobots or nanobots that enter the cells and manipulate the process inside and treat dreadful diseases like cancer. From the last two decades researchers around the world are trying in different ways to make that vision into a reality. Looking for the possible invention with the novel materials under synthesis, the researchers from at PennState university, USA has showed a considerable progress. They synthesized nanobots made of Gold-ruthenium bimetal nanorods. The functionality of the nanorods is their spinning behaviour in the presence of ultrasonic fields. This makes the rods behave as the small tiny nanomotors.

"This research is a vivid demonstration that it may be possible to use synthetic nanomotors to study cell biology in new ways. We might be able to use nanomotors to treat cancer and other diseases by mechanically manipulating cells from the inside. Nanomotors could perform intracellular surgery and deliver drugs non-invasively to living tissues." 

- Evan Pugh, Professor of Material Chemistry and Physics, PennState.

The researchers studied the nanomotors working in HeLa cells. They gave the nanomotors into the medium given to the HeLa cells. The cells uptake the nanomotors. The nanomotors work very little when a lower ultrasonic frequency waves were given the actual working of these nanomotors was observed at higher ultrasonic frequencies. A series of videos demonstrating the uptake of the nanomotors and the cells in action in the link given below.

http://phys.org/news/2014-02-nanomotors-cells-video.html#jCp

The research in combating cancer exploring different unique ways where the conventional therapies are not enough. It is the vision of any science-fiction lover to have nanorobots killing cancer cells one by one. I think we are at the age where the technology is highly advancing where with the help of nanotechnology we can actual make the science-fiction things possible and real. We hope the answer for the cancer treatment is not so far.

Courtesy:http://www.phys.org.

Nanochains for the treatment of Cancer Micrometastasis

Cancer is the well known diseased state around the world with millions of people suffering from it. For researchers it is a heap of task to combat this disease. From several decades several treatment methods are in practice. Among them, surgery and chemotherapy are the highly recommending treatment methods. Physicians remove the tumor through surgery and then suggest the high dosage of tumor suppressing drugs also called chemotherapy. These methods can be followed when the tumor size is around 100 mm³, provided the tumor is benign and not metastatic.

What is with the metastatic tumor? The cancer cells detach from the solid benign tumors migrate to different organs in the body and grow into tumors. This state is called metastatic state. The cancer at this stage is highly resistant to treatment. It is difficult to remove the numerous tiny tumors by surgery because the size of these metastatic tumors is very less. Normally more lethal cancer like pancreatic cancer will be in metastatic stage by the time the physician detect the presence of cancer. Thus the treatment is very difficult and the chances of survival also very very less. Thus the mortality rate increases.

Researchers are trying different methods and novel materials to treat this kind of metastatic cancer. With the availability of the high end technology like nanotechnology, where the nano (10^-9m) sized materials are synthesized and exploited for different applications, there is scope to find some novel ways of treatment. A recent paper in Journal of controlled release during the january issue showed the new kind of nanomaterials called as nanochains are employed to treat the cancer state. The nanoparticles were loaded with drug and linked to the other nanoparticle by a covalent linkage. The authors found that these materials are highly penetrable to the deep locations of the tumor and releasing the drug will kill the cancer cells. Novel materials like these are crucial to combat diseases like cancer.

Reference: Journal of controlled release, vol. 173, 10 January 2014, Pages 51–58

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.

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

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. 

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.