Nanomedicine - Future Medicine (Part I)
The potential of Nanomedicine: why is small different?
To manipulate matter locally and deliberately on the atomic/molecular scale is an old dream of natural science. Starting in 1959 with the famous talk of Richard Feynman at the annual meeting of the American Physical Society where he developed the vision of manipulating and controlling things on a small scale, nanoscience developed over the discovery of the molecular beam epitaxy in 1968 in the Bell Laboratories, the generation of nanoparticles and the invention of the Scanning Tunnel Microscope (STM) to a robust and well accepted field in the scientific community. The old dream became already true in the field of today’s nanoscience and nanotechnology, opening novel opportunities in virtually all branches of technology ranging from optical systems, electronic-, chemical- and automotive industry to environmental engineering and medicine. Smart surface coatings, intelligent nanoscale materials, faster electronic, unprecedented optics, biosensors, and nanomotors are just a few examples from this transdisciplinary area, and although nanotechnology is still in its infancy, these first practical applications clearly demonstrate its enormous potential.
The potential of Nanomedicine: why is small different?
The application of nanotechnology for medical purposes has been termed nanomedicine and is defined as the use of nanomaterials for diagnosis, monitoring, control, prevention and treatment of diseases (Tinkle et al., 2014). However, the definition of nanomaterial has been controversial among the various scientific and international regulatory corporations. Some efforts have been made in order to find a consensual definition due to the fact that nanomaterials possess novel physicochemical properties, different from those of their conventional bulk chemical equivalents, due to their small size. These properties greatly increase a set of opportunities in the drug development; however, some concerns about safety issues have emerged. The physicochemical properties of the nanoformulation which can lead to the alteration of the pharmacokinetics, namely the absorption, distribution, elimination, and metabolism, the potential for more easily cross biological barriers, toxic properties and their persistence in the environment and human body are some examples of the concerns over the application of the nanomaterials
Video: Courtesy of Nanomedicine European Technology Platform
Nanomedicine is the application of nanotechnology to achieve innovation in healthcare. It uses the properties developed by a material at its nanometric scale 10-9 m which often differ in terms of physics, chemistry or biology from the same material at a bigger scale.
Moreover, the nanometric size is also the scale of many biological mechanisms in the human body allowing nanoparticles and nanomaterials to potentially cross natural barriers to access new sites of delivery and to interact with DNA or small proteins at different levels, in blood or within organs, tissues or cells.
At the nano-scale, the surface-to-volume ratio is such that the surface properties are becoming an intrinsic parameter of the potential actions of a particle or material. Coating of the particles and functionalization of their surfaces (even on multiple levels) are in this way extremely common to increase the biocompatibility of the particle and its circulation time in the blood, as well as to ensure a highly selective binding to the desired target.
Figure: Nanomedicine impacts all fields of medicine. Courtesy of Nanomedicine European Technology Platform
Nanomedicine has the potential to enable early detection and prevention and to drastically improve diagnosis, treatment and follow-up of many diseases including cancer but not only. Overall, Nanomedicine has nowadays hundreds of products under clinical trials, covering all major diseases including cardiovascular, neurodegenerative, musculoskeletal and inflammatory. Enabling technologies in all healthcare areas, Nanomedicine is already accounting for approximatively 80 marketed products, ranging from nano-delivery and pharmaceutical to medical imaging, diagnostics and biomaterials.
Nanomedicine includes the development of nanoparticles, nanostructured surfaces and nanoanalytical techniques for molecular diagnostics, treatment, follow up and therapy of diseases (theranostics), as well as integrated medical nanosystems, which, in future, may perform monitoring and complex repairs in the body at the cellular level. Nanotechnology considers cells as a complex system of interacting nanoengines. Visionary concepts suggest the construction and control of artificial cells using engineered nanodevices and nanostructures for medical applications.
Figure: Nanoparticles
Within Biotechnology I have had the opportunity to meet many important researchers over 18 years organizing Nanotechnology events. I would like to introduce you to one of them that I have chosen for his research work. His name is Dr. Avi Schroeder and he works at Targeted Drug Delivery and Personalized Medicine Group, Technion, Israel. Here is a short biography and an abstract of his research.
Bio: Head of the Targeted Drug Delivery and Personalized Medicine Group, Technion, from 2012. Postdoctoral Studies 2009 - 2012, MIT, Cambridge. Ph.D. 2009, Ben-Gurion University
Research Fields: Our research group is aimed at improving patients’ quality of life and bettering their treatment by developing innovative medical technologies.
Specifically, we will focus on targeting metastatic cancer with nanotechnology, and on constructing miniature medical devices that couple diagnosis to therapy (theranostic devices).
Research Topics
Personalized Cancer Treatment
Patient-specific biomarkers have helped to advance personalized medicine, however, much remains unknown when predicting whether a certain patient will or will not respond to therapy. In our lab, a nanoparticle-based technology for predicting the therapeutic potency of drugs is developed. Once a tumor is detected, a cocktail of DNA-barcoded nanoparticles, each containing a different drug, is injected intravenously. The particles accumulate in the various cells that compose the tumor microenvironment, utilizing the enhanced permeability and retention (EPR) effect. After enabling each of the drugs to take action, a biopsy is taken from the tumor and the tissue is homogenized, to form a single-cell suspension. After sorting the cells according to cell type and to their live/dead viability state (potency screen), the DNA barcodes are extracted from the cells and the cell viability data is correlated with the type of drug/s found inside each of the cells, thereby identifying which drug or drug combination is optimal for treating the lesion. Based on the screen, a treatment protocol can be selected for the patient. Selecting a proper therapeutic that will address each patient’s unique disease presentation, can significantly improve the treatment course and outcome.
Synthetic Cells
Synthetic cells are an emerging scientific field that holds promise to transform engineered tissue into a bionic state, analogous to the technological transformation from walking or horses-and-buggies to cars and airplanes. In our research, synthetic cells are evaluated as autonomous systems for producing therapeutic proteins inside the body. Synthetic cells can exceed certain natural functions, such as producing only one protein at large amounts, or producing therapeutic proteins that are toxic to living cells. The versatile characteristics of synthetic cells will allow tailoring biologics for the personalized needs of each patient.
Targeting Tumor Microenvironment
Cancer cells need the support of other cells to progress to a tumor. Without this supporting environment, the so-called tumor microenvironment, cancer cells cannot grow. Currently, most of treatment strategies focus on killing the cancer cells. Our approach is to treat and target the supportive environment. We believe that combined targeting of the microenvironment and the tumor cells can enhance disease control and patient survival. We are designing liposomes that can carry both chemotherapeutic agents, which kill the cancer cells, and other small molecules that are aimed to attack the microenvironment. Moreover, we design liposomes that interfere with primary metabolic processes of the tumor microenvironment, including acidification, by delivering alkaline buffers to the tumor and improving chemotherapeutic agents’ activity.
Proteolytic Protein Delivery
Surgical blades are common medical tools. However, they cannot distinguish between healthy and diseased tissue, thereby creating unnecessary damage and increasing pain. We engineered nanoparticles that contain a controllable activated proteolytic enzyme. Once placed at the surgical site, the enzyme is released and activated by its co-factor, thus starting its proteolytic activity. This system was used to replace a surgery for teeth alignment, and for relaxation of the fibrotic stroma barrier that surrounds pancreatic tumors.
Targeting Metastasis
Despite advances in cancer therapy, treating cancer after it has metastasized remains an unmet clinical challenge. Common therapeutic options become limited when dealing with metastases. In our lab, we assessed the ability of liposomal nanoparticles to target triple-negative breast cancer (TNBC) metastases in vivo. We studied the effect of several disease conditions on nanoparticle accumulation at the metastatic site, including the size of the metastases, the presence or absence of a primary tumor alongside the metastases, and the size of the metastatic lesion. Interestingly, we observed that nanoparticles may also be found in elevated levels in the pre-metastatic niche, several days before metastases are visualized by MRI or histologically in the tissue.This highlights the promise of diagnostic and therapeutic nanoparticles for treating metastatic cancer, possibly even for preventing the onset of the metastatic dissemination by targeting the pre-metastatic niche.
Agricultural Nanotechnology
There is a world-wide need for efficient agricultural technologies. The use of drug delivery systems enables treatment by overcoming biological barriers and enhancing drug targeting to diseased tissues. In our lab, we load agricultural nutrients intro nanoscale drug-delivery systems and apply them to the leaves of tomato plants. We show that liposomes are internalized by plant cell and release their encapsulated payload. Tomato plants treated with liposomes loaded with Fe and Mg overcame acute nutrient deficiency which was not treatable using ordinary agricultural nutrients. We also interested in aquaculture and demonstrated a use of nanoparticles loaded with anti-viral RNAi in shrimp’s disease protection.
The nanometer – 10 to the -9th meter- is a miniscule unit representing the world of nanoscience and nanotechnology, a field which is sometimes unknown but which has visible effects. With the aim of discovering what happens in the nanoworld and see what is being done in the fields of research and technology at a small scale, from April , the sixth edition of the Nanoscience and Nanotechnology Fest ival 10alamenos9 (www.10alamenos9.es) will take place.
The new edition of the festival, coordinated by the University of Barcelona, has more than a hundred activities, doubling the number of activities from last year’s edition. Fifty entities are taking part in the organization –universities and research institutes-, lots of them being reference entities in Iberoamerica in the field of nanotechnology.
The event is sponsored by BASF. Every year many (8) Iberoamerican countries organizes an outreach Festival with many activities, for example, this contest (https://icmab.es/concurs-de-nanorelats-organized-within-the-10alamenos9-festival). This event will take place in nine cities in Spain and other countries from April to May with activities aimed at the general public and schools, and it will have more than 5,000 participants.
The aim is to bring nanoscience and nanotechnology closer to people in a dynamic, fun and rigorous way and show people that nanotechnology is a reality, which is not seen but it is all over.
In Barcelona, there will be activities aimed at primary and secondary education schools –through the Nanoinventum/NAnoEduca project- apart from exhibitions, some with nanotechnology products and augmented reality, and seminars carried out by distinguished researchers, as well as workshops that are related to the several fields of nanoscience.
The Festival reaches its sixth edition from 2015. We made also some online activities possible such as the "Vermut de nanociència" with the main objective of bringing nanotechnologies to everybody in an understanding way and broadcasting it in streaming to make easier the participation and the debate. The talks started on April and ended on May. Last year we made 33 videos.
We are in touch
https://icn2.cat/en/outreach/education-program/10alamenos9
https://icmab.es/more-than-200-students-at-the-10alamenos9-nanoscience-and-nanotechnology-festival-at-uab-campus
For 18 years I have been and still am the contact person for the Spanish Nanotechnology Network (Nanospain) and this has encouraged me to start writing in this newsletter. I have had the opportunity to meet first hand Spanish and foreign researchers whose research revolves around Nanotechnology.
I hope you enjoy it. I will try to publish one post per week.
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