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 

Multifunctional Nanomaterials in Nanomedicine

After a long gap I am writing another post in my blog.  In this post I wish to write about the work I am doing. The viewers should know what the "Nanotechnologist" is upto. Luckily, I have published two research papers this year and I wish to discuss them. I discuss now my first paper in this post and the discussion about the second paper follows this post.

As from my profile, everyone knows that I am doing Ph.D in SASTRA University, Thanjavur, one of the finest institutions for nanotechnology research. I am working on theranostic multifunctional nanomaterials for cancer treatment. In my first paper, I synthesized the multifunctional nanomaterial and tested against cancer cells, retinoblastoma. The paper was published in Journal of Biomaterial science, polymer edition. Due to the journal copy right issues, i can't attach the hard copy of the paper to this post, i am including the reference of the paper at the bottom of this post.

Combating cancer with a single weapon, say chemotherapy, is not sufficient. Physicians suggesting combination therapies such as chemotherapy with radiation treatment. So combination treatments are giving results. The drawback is that giving high doses of chemo and radiation to patient leads to several side effects, like losing hair is the common scene observed in case of radiation treated patients. To improve the patients quality of life with minimal side effects or none, new technologies have to be tested and used.

One such technology is the utilization of nanomaterials in medicine to treat diseases like cancer. Nanomaterials are those confined to the size of nanometer (10-9m). In case of nanomedicine the horizons with respect to length differ slightly. Many nanomaterials tested for medical applications vary from 10 nm to 400 nm approx. The nanomaterials which are usually the delivering vehicles called as carriers (nanocarriers) deliver drug to the target cells. The end goal is that these materials should be used for imaging, and treating of cancer at the same time. The concept of multifunctionality should be imposed into the nanocarrier. 

Multifunctional Nanomaterial

The manuscript entitled "Engineered multifunctional nanomaterials for multimodal imaging of retinoblastoma cells in vitro" studied the imaging of cancer cells using MRI (Magnetic resonance imaging)  and fluorescence. This property helps in tracking the cancer cells non invasively. SPIONs (superparamagnetic iron oxide nanoparticles) with high magnetization and good senstitivity in MRI were synthesized. The nanoparticle surface was modified with oleic acid and again coated with bovine serum albumin and decorated with sulforhodamine B, fluorescent dye. This material showed no toxicity towards healthy cells. The MRI and fluorescence imaging abilites were studied.

The multifunctional nanomaterials are highly useful in imaging the cancer cells in vivo which helps in better diagnosis and progressively better treatment of cancer.

Reference: Leela Raghava Jaidev, Dhiraj Vasanth Bhavsar, Uma Sharma, Naranamanglam R. Jagannathan, Uma Maheswari Krishnan & Swaminathan Sethuraman (2014) Engineered multifunctional nanomaterials for multimodal imaging of retinoblastoma cells in vitro, Journal of Biomaterials Science, Polymer Edition, 25:11, 1093-1109.

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

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.