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Nanomedicine entering mainstream to treat Cancer, HIV and Chem-Bio weapon threats.

Nanomedicine is a branch of medicine that applies the knowledge and tools of nanotechnology to the prevention and treatment of disease. Nanomedicines typically encapsulate therapeutic and/or imaging compounds in submicrometer-sized carrier materials. Nanomedicine involves the use of nanoscale materials, such as biocompatible nanoparticles and nanorobots, for diagnosis, delivery, sensing or actuation purposes in a living organism. Billions of dollars have been invested by USA, Japan and China into nano research, for uses including both military and industry.

 

The use of nanotechnology in medicine has the potential to have a significant impact on human health by improving the diagnosis, prevention and treatment of diseases. Nanomedicines are generally intended to increase the therapeutic index of compounds by allowing more efficient delivery to the target site to enhance therapeutic efficacy and/or by minimizing accumulation in healthy body sites to reduce toxicity.

 

It was more than 20 years ago when the U.S. Food & Drug Administration approved the first nanoparticle drug, Doxil. Doxil encapsulates the cancer drug doxorubicin in a lipid sphere called a liposome. Since that decision in 1995, FDA has approved several other nanoparticle formulations. Nanomedicine is now making great strides, and, nanoparticles are already being used to target disease at the cellular and even molecular level.

 

Nano-enabled medical products began appearing on the market over a decade ago. The main therapeutic areas they have impacted are cancer, CNS diseases, cardiovascular disease and infection control. While nano-enhanced drug delivery products are a commercial reality, more advanced nanotech-based medical devices remain in development, although some are at the clinical testing stage. Some of the recent exciting developments in the world of nanomedicine have been delivering chemotherapy drugs directly to cancer cells, delivering HIV drugs at lower doses with the same effect, attacking fungal infections and regenerating human organs without the controversial use of embryonic stem cells.

Nano-bots are currently being tested for the treatment of blood clots and oxygen transportation around the body. These blood cells or platelet functions have not yet been achieved but are highly anticipated nano-healthcare solutions. One major challenge of Nanorobotics is that of tracking and safe removal of the robots once they are done.

 

Nanomedicine benefits

Nanoparticles can interact with cells, bacteria and viruses in a very intimate and efficient way because they present a similar size than these biological entities. This close interaction has been exploited for achieving important abilities such as the selective transport of drugs directly to diseased cells and tissues

Disease Diagnosis

Nanomedicine is expected to deliver real improvements in quick diagnosis of the diseases much earlier by detecting problems at the molecular level. By using nanotechnologies to study and identify individual molecules, healthcare professionals can diagnose diseases in time to improve the patient’s prognosis; and by using nanomedicines to treat them the outcome can also be improved.

Personalized Medicine

As healthcare moves from a one-size-fits-all treatment approach to more personalised care based on an individual’s genetics and immune responses, nanomedicine is going to be the key to providing the tailored treatment that will improve patient care.

 

Detecting Heart Attacks

Studies on heart attack have detected a recurring trait that is now linked as a precursor. Using a wireless transmitter nano-bot in the bloodstream, the amount of arterial slough coming off the heart walls can be used to track the possibility of a heart attack coming on.

 

Bacteriology

Nanoscience is being used to design silicon insects modelled after naturally occurring insects that have the antibiotic properties of these organisms. Antibacterial nanotechnology is not limited to silicon materials as some researchers now use gold particles and molecules for antibacterial treatment. Bacteria are also being employed to transport nano-robots to specific sites for use.

 

Wounds

The use of nano-electric pulses enabled by nanogenerators in bandages is being researched for treating open wounds. These pulses seem to improve the time it takes for these wounds to heal. But, nanoscience doesn’t just work for external wounds or surgeries. The case is being made for internal injuries and bleeding by a lecturer from Case Western University whose research is on developing nanoplatelets.

 

Nano-robots

These are intrinsic in diagnostics and disease management as they have access to various parts of the body that external diagnostics can barely reveal. For cancer research, this breakthrough translates to faster detection and easier trackings of treatment progress.

 

Most notable application if nano-robotics in treating cancer is for delivery of chemotherapy to the specific cancer cells without the attendant immuno-suppression that comes with the general application of chemotherapy. If Chemotherapy can be safely delivered to cancer cells, the costs; financially and healthwise, of multiple chemotherapy sessions will be greatly reduced and productivity multiplied.

 

Nanomedicine for Cancer

As cancer is one of the biggest health challenges facing humanity, a substantial amount of research has focused on nanomaterials as drug delivery agents to target cancer tissues, as illustrated by almost 12,000 manuscripts in the recent decade. The conventional treatment of cancer is based on three strategies: surgery, radiotherapy and chemotherapy. These approaches exhibit a lack of selectivity affecting also the surrounding healthy tissues, in the case of surgery and radiotherapy, and/or to the whole organism, in the case of chemotherapy.

 

Nanomedicine represents an efficient drug delivery system, which can deliver cytotoxic agents with higher drug content  to transport them in the blood stream and finally, to recognize the tumoral tissue and release their cargo  directly to the targeted cancer cells only and minimize the dose-dependent side effects of drugs on nontarget sites.  Once the nanoparticle reaches the tumoral area, it faces a complex scenario. Tumoral masses are not composed by an homogeneous tumoral cell distribution but they are formed by a myriad of different cell populations, from tumoral cells to immune, supportive and healthy cells of the original tissue .

 

Therefore, nanoparticles should possess the capacity to recognize the malignant cells and focus the effect onto them in order to achieve an efficient therapeutic effect. This ability can be incorporated in the nanodevice by anchoring targeting moieties on the particle surface

 

Nanoparticles deliver chemotherapy drugs directly to cancer cells

A number of nanoparticle chemotherapy drugs have been developed in recent years, a number of which have had success in lung cancer as well as other tumor sites. The first of these to be approved for non-small cell lung cancer (NSCLC) is Abraxane, or albumin-bound paclitaxel.

 

Hoopes’s group uses iron oxide nanoparticles coated with biocompatible substances to treat cancer. Once inside the tumour, the iron oxide nanoparticles can be heated using an alternating magnetic field, killing it with little damage to the surrounding tissue. They are applying their technique to treat Breast cancer that has proved an ideal target for magnetic nanotherapy. The tumours are accessible, easily imaged and localised, and often spread to lymph nodes, where nanoparticles tend to accumulate when injected into the bloodstream.

 

Chinese Scientists deliver drug directly to Nucleus of cancer cells

Scientists in China have developed an intelligent nanoparticle system that delivers a chemotherapeutic and radiosensitiser drug directly to the nucleus of cancer cells. Tests suggest this intranuclear radiosensitisation technique could intensify the effects of radiotherapy.

 

Central to their system is a new generation of fluorophores called upconversion nanoparticles that convert low energy near infrared radiation into higher energy visible radiation – they are therefore ideal imaging probes. Mesoporous silica containing upconversion nanoparticles were covalently tagged with an amino acid sequence to direct them into the nucleus. A chemotherapeutic and radiosensitising drug called mitomycin C was also attached.

 

In recent years, scientists have turned their attention to theranostics in a bid to develop multifunctional therapeutic options that diagnose and treat target cells simultaneously. ‘This study illustrates the principle of the “detect-to-treat” strategy and proves highly valuable for various cancer theranostic applications, thus finally fulfilling the ultimate goal of “one drug fits all”,’ explains Shawn Chen, a leading theranostics expert at the National Institute of Health, US

Innovative Light Therapy Reaches Deep Tumors

Light long has been used to treat cancer. But phototherapy is only effective where light easily can reach, limiting its use to cancers of the skin and in areas accessible with an endoscope, such as the gastrointestinal tract.Using a mouse model of cancer, researchers at Washington University School of Medicine in St. Louis have devised a way to apply light-based therapy to deep tissues never before accessible. Instead of shining an outside light, they delivered light directly to tumor cells, along with a photosensitive source of free radicals that can be activated by the light to destroy cancer. And they accomplished this using materials already approved for use in cancer patients.

 

“Phototherapy works very well and has few side effects, but it can’t be used for deeply embedded or metastatic tumors,” said senior author Samuel Achilefu, PhD, professor of radiology and of biomedical engineering at Washington University. “In general, shining a light on photosensitive materials generates free radicals that are very toxic and induce cell death. But the technique has only worked well when light and oxygen can get there. The need for oxygen and the shallow penetration of light in tissue have limited advances in this area for decades.”

Tiny Quantum Dots wipe out infectious bacteria without harming healthy cells

Recent years have seen many diseases and disorders develop a resistance to antibiotics and other drugs traditionally used to treat them, these traditional medicines also suffer from poor absorption by body to gain any benefit from them and also create side effects on the other healthy organs and tissues.

 

Scientists of Colorado University have developed light-activated nanoparticles and shown in lab tests that these “quantum dots” are more than 90 percent effective at wiping out antibiotic-resistant germs like Salmonella, E. coli and Staphylococcus. “In our study, we tailored these quantum dots so they can selectively kill these ‘superbugs’ without affecting other host mammalian cells (or human cells),” Dr. Prashant Nagpal, assistant professor of chemical and biological engineering at the University of Colorado at Boulder and a leader of the research, told The Huffington Post in an email.

 

While traditional nanoparticles made of metals like gold and silver can be harmful to healthy tissue as well as the target bacteria, the new quantum dots made of semiconducting materials like cadmium telluride do not harm the healthy cells. Moreover they can be tailored to specific infections, slipping inside the disease-causing germs and, when activated by light, triggering chemical reactions that destroy them. “We don’t use any special light, and a typical weak light source (a lamp, well-lighted room, sunlight, etc.) is enough to activate these quantum dots,” Nagpal said in the email.

 

Researchers’ forsees many application of these quantum dots, depending on the nature of the infection, Infected cuts might simply be covered with nanoparticle-impregnated bandages, Patients with systemic infections might receive injections of quantum dots. In addition, hospital rooms and medical instruments might be treated with a dot-containing disinfectant in order to reduce the risk of spreading infections from patient to patient. But more research, including clinical trials, will be needed to develop quantum dot therapy and prove its safety and effectiveness in humans. Nagpal said he was seeking funding from federal agencies or private donors to make that happen.

 

Other Diseases

A large number of brain disorders with neurological and psychological conditions result in short-term and long-term disabilities. Recent years observed a significant number of research studies being published on methods for the synthesis of nanoparticle-encapsulated drugs within in vivo and in vitro studies. The insufficient absorbance of oral drugs administered for a range of neurological conditions, such as Alzheimer’s disease, Parkinson disease, tumor, neuro-AIDS, among others, opens up the necessity of nanomedicine with stem cell therapy. Some of the registered nanoparticles for the complex CNS treatment are a gold nanoparticle, lipid nanoparticle, and chitosan nanoparticles.

 

At the University of Liverpool, Andrew Owen, professor of pharmacology, in collaboration with Steve Rannard, professor of chemistry,are working on solid drug nanoparticle formulations of HIV drugs which are better absorbed into the body, leading to reduced amount of drug required per patient for effective therapy or more people could be treated with the drugs available.

 

Researchers from the Institute of Bioengineering and Nanotechnology in Singapore, working with a team from IBM on project nicknamed ‘Ninjas vs Superbugs’, have used an organic catalytic process to engineer the plastic bottles into non-toxic, biocompatable, nanofibre molecules to attack fungal infections that have become antibiotic resistant. Their new nanomedicine can target and kill off just the infected fungi cells by creating an electrical charge on the nanoparticles which is attracted only to the fungi cells.

 

A team of researchers at the University of Manchester’s Nanomedicine Laboratory, are using nanomedicine for regenerative medicine. Professor Kostas of the laboratory induced somatic cells in the livers of adult mice to transiently behave as iPS cells, using non-viral, transient, rapid and safe methods. It involves injecting large volumes of plasmid DNA to reprogram the cells and, as the plasmid DNA is short-lived, the risk of uncontrolled growth into tumours is reduced.

 

Versatile particles offer a wide variety of diagnostic and therapeutic applications

Kit Lam and colleagues from UC Davis have created versatile nanoparticles (NPs) that can be used as contrast agents to light up tumors for MRI and PET scans or deliver chemo and other therapies to destroy tumors.”These are amazingly useful particles,” noted co-first author Yuanpei Li, a research faculty member in the Lam laboratory. “As a contrast agent, they make tumors easier to see on MRI and other scans. We can also use them as vehicles to deliver chemotherapy directly to tumors; apply light to make the nanoparticles release singlet oxygen (photodynamic therapy) or use a laser to heat them (photothermal therapy) – all proven ways to destroy tumors.”

 

Jessica Tucker, program director of Drug and Gene Delivery and Devices at the National Institute of Biomedical Imaging and Bioengineering, which is part of the National Institutes of Health, said the approach outlined in the study has the ability to combine both imaging and therapeutic applications in a single platform, which has been difficult to achieve, especially in an organic, and therefore biocompatible, vehicle.

 

Though not the first nanoparticles, these may be the most versatile. Other particles are good at some tasks but not others. Non-organic particles, such as quantum dots or gold-based materials, work well as diagnostic tools but have safety issues. Organic probes are biocompatible and can deliver drugs but lack imaging or phototherapy applications. Built on a porphyrin/cholic acid polymer, the nanoparticles are simple to make and perform well in the body. Porphyrins are common organic compounds. Cholic acid is produced by the liver. The basic nanoparticles are 21 nanometers wide (a nanometer is one-billionth of a meter).

RNA to build controllable and defined nanostructures for material and biomedical applications

RNA is a polymer by nature. Recent technological advances to make RNA chemically and enzymatically stable and the discovery of unusual thermostability of some RNA motifs, as well as important biomedical applications have propelled the concept of RNA as a polymeric building block into a new horizon.

 

“RNA can serve as a unique polymeric material to build varieties of nanostructures including nanoparticles, polygons, arrays, bundles, membrane, and microsponges that have potential applications in biomedical and material sciences,” write authors Hui Li , Taek Lee, and others in their review paper.Biological macromolecules, as natural building blocks, are critical for the functioning of living organisms. RNA is one of the five most important biological macromolecules in addition to DNA, proteins, lipids and carbohydrates.

 

“The value of polymers is manifested in their vital use as building blocks in material and life sciences. It is expected that applications of RNA as a polymer and as building blocks will appear more and more in therapeutics, detection, sensing, nanoelectronic devices, and other polymer industries. ”

 

“The anion nature, the thermodynamic stability, the insulating property, the self-assembly capability and other novel features such as versatility, molecular-level plasticity, as well as the potential semiconductor behavior will make RNA unique for exploring new scientific territories. RNA has been shown to be major components of cells and leading functionality of life, and it is expected that RNA will also be the momentous material of daily life in the future.”

Challenges of nanomedicine

However  a recent review paper questions the efficacy of current nanoparticles to target drugs to tumors.The authors reviewed the nanoparticle delivery literature from the past decade and estimated that the median delivery efficiency is low—only 0.7% of an injected dose of nanoparticles ends up in a tumor (Nat. Rev. Mater. 2016, DOI: 10.1038/natrevmats.2016.14). This low efficiency, the authors argue, is a hurdle for translating nanomedicines into the clinic. They propose a 30-year plan to study the delivery problem in detail to help improve efficiency. “The paper has caused quite a storm,” says Scott E. McNeil, director of the Nanotechnology Characterization Laboratory (NCL) at the U.S. National Cancer Institute.

 

With the rapid growth in the use of nanomaterials for medical applications, the most urgent need is developing and validating novel and practical approaches that are able to determine potential short-term and long-term health risks. Accomasso et al. summarized the current state regarding the safety evaluation of nano-based therapeutics and discussed the importance of risk assessment and risk minimization in the development of nanomedicines.

 

The experimental development of nanomedicines is continually progressing at a fast pace, however significant challenges still exist in promoting these platforms into clinically feasible therapies. Key issues related to the clinical development of nanoparticulate nanomedicines include biological challenges, biocompatibility and safety, large scale manufacturing, government regulations, intellectual property (IP), and overall cost-effectiveness in comparison to current therapies.

 

Military and Security Applications

Chemical and Bio Defense

The Defense Threat Reduction Agency’s Chemical and Biological Technologies Department (DTRA CB) is looking to fund S&T for improved detection, protection, and countermeasures against chemical and biological threats. One of Its major thrust is Nanostructured Active Therapeutic Vehicles (NATV) program to develop nanostructured material vehicles capable of active detection of chemical and biological threats and release of in vivo therapeutic payloads in prophylactic or presymptomatic administration of targeted therapies.

 

 DARPA

DARPA desires to develop versatile “platform capable of rapidly synthesizing therapeutic nanoparticles” to target unknown, evolving and even genetically engineered bioweapons. Darpa would like to see nanoparticles loaded with “small interfering RNA (siRNA)” — a class of molecules that can target and shut down specific genes. If siRNA could be reprogrammed “on-the-fly” and applied to different pathogens, then the nanoparticles could be loaded up with the right siRNA molecules and sent directly to cells responsible for the infection.

 

DARPA  is making a long-shot request for an all-out replacement to antibiotics, the decades-old standard for killing or injuring bacteria to demolish a disease. In its place: the emerging field of nanomedicine would be used to fight bacterial threats. The agency’s “Rapidly Adaptable Nanotherapeutics” is after a versatile “platform capable of rapidly synthesizing therapeutic nanoparticles” to target unknown, evolving and even genetically engineered bioweapons.

 

Malone, Brett (Pearisburg, VA, US)  and Bryson, Joshua (Blacksburg, VA, US) have been granted patent on “Rapidly Adaptable Nano Therapeutics for Treatment of Infectious Disease”.The invention relates to rapidly adaptable nanotherapeutics. The therapeutics are nucleic acid molecules, such as, RNA, DNA, or modified-DNA. The nucleic acid therapeutics are preferably administered as a nanoparticle composition, further containing one or more synthetic polymers.

 

The therapeutics are rapidly adaptable because the identification and design of the polynucleotide sequence containing the therapeutic sequence is based upon rapid computer-implemented bioinformatics and nucleic acid synthesis protocols. The rapid adaptable protocols differ from traditional methods of antibiotic and antipathogenic drug development, which are slow and do not address drug resistance issues. Furthermore, the invention encompasses a facility with dedicated apparatus for practicing the invention in military theater or where emerging pathogenic threats are located. This facility may be mobile and transportable as a dedicated unit.

Big Market Growth in Nanomedicine

The global nanomedicine market is anticipated to reach USD 350.8 billion by 2025. Therapeutics accounted for the largest share of market revenue in 2016 owing to presence of nanoemulsions, nanoformulations, or nanodevices
These devices possess the ability to cross biological barriers. North America dominated the industry in 2016, accounting for a 42% of total revenue. Moreover, presence of drugs such as Doxil, Abraxane, and Emend is attributive for higher revenue generation.

 

Market drivers for nanomedicine product development include unmet medical needs such as direct targeting of diseased tissue, early diagnosis of cancer, transport of drugs across the blood-brain barrier and development of implant materials with longer lifespans. Nanomedicine sets out to contribute to overcoming these problems in concert with other medical technologies such as biopharmaceutical drugs, cell therapy and gene therapy. Thus nanotechnology is only one of several drivers for innovation in medicine.

 

“An increasing use of nanobiotechnology by the pharmaceutical and biotechnology industries is anticipated. Nanotechnology will be applied at all stages of drug development – from formulations for optimal delivery to diagnostic applications in clinical trials.” Some of the earliest applications are in molecular diagnostics. Nanoparticles, particularly quantum dots, are playing important roles. In vitro diagnostics, does not have any of the safety concerns associated with the fate of nanoparticles introduced into the human body.

 

 

Drug delivery remains a near-term opportunity for medical nanotechnology, with diagnostics as the second major opportunity in the immediate future. With the latter, biochip developments and nanobiotechnology have contributed significantly to segment growth.

 

The most important pharmaceutical applications are in drug delivery. Apart from offering a solution to solubility problems, nanobiotechnology provides and intracellular delivery possibilities. Skin penetration is improved in transdermal drug delivery. A particularly effective application is as nonviral gene therapy vectors. Nanotechnology has the potential to provide controlled release devices with autonomous operation guided by the needs. Numerous nanodevices and nanosystems for sequencing single molecules of DNA are feasible. Various nanodiagnostics that have been reviewed will improve the sensitivity and extend the present limits of molecular diagnostics.

 

Key players operating in this industry include Pfizer Inc., Ablynx NV, Nanotherapeutics Inc., Nanoviricides Inc., Abraxis Inc., Arrowhead Research Inc., Celgene Corporation, Bio-Gate AG, and Merck

 

 

 

 

About Rajesh Uppal

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