Blood Brain Barrier
Neurodegenerative diseases are considered a big challenge for nanomedicine since a big limitation to treat them is to reach the central nervous system. For that, nanoparticles must cross the protective Blood Brain Barrier (BBB), which has a size and molecular cut off that limits most nanoparticles from penetrating at therapeutically relevant doses. Therefore, the development of an improved delivery system to achieve brain targeting and neuronal uptake is urgently needed.
In our lab, we are focused in developing brain-targeted liposomes able to deliver biological therapeutics such as monoclonal antibodies, proteins or nucleic acids, and to cross the BBB in an efficient manner to treat neurodegenerative diseases. We are evaluating the capacity of the designed liposomes to stop the progression of parkinson disease by reducing the aggregation of alpha-synuclein, the main responsible of neuronal death. The demonstration of the liposomes’ efficacy will provide a great alternative for treating different neurodegenerative diseases by modifying the liposomal payload.
We showed that cancer cells have a symbiotic relationship with nerve cells. In fact, breast cancer cells recruit the surrounding nerve cells to infiltrate tumors and stimulate their growth. Therefore, we have developed anesthetic nanoparticles that target the neurons within breast cancer tumors and interrupt their communication with the cancer cells. As a result, we managed to curb tumor growth and metastasis formation
Personalized Cancer Treatment
Selecting a proper therapeutic that will address each patient’s unique disease presentation, can significantly improve the treatment outcome. 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. This technology will improve care by personalizing the treatment course for each patient.
Synthetic cells, artificial cell-like particles with a bottom-up design, offer great potential to support malfunctioning cells inside the body. Developing synthetic cells for therapeutic use is 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 in large amounts or producing therapeutic proteins that are toxic to living cells. As part of our research, we explore the potential use of synthetic cells in different biomedical fields such as regenerative medicine and cancer. In addition, we develop regulated communication mechanisms between synthetic cells to natural cells and between synthetic cells to themselves, for example, through light.
Combining the disciplines of biology and engineering to address unmet medical needs makes synthetic cells attractive therapeutic platforms. Furthermore, synthetic cells also enable exploration of the origins of life and understanding the minimal requirement for cellular life to exist. The versatile characteristics of synthetic cells will allow tailoring biologics for each patient's personalized needs
Evolving climate change and increasing world population calls for efficient, state-of-the-art agricultural technologies to reduce food waste and advance crop protection. The use of drug delivery systems enables treatment by overcoming biological barriers and enhancing drug targeting to diseased tissues.
In our lab, we develop an innovative approach for treating viral diseases in agriculture using RNAi nanotechnology. Specifically, we curb the devastating impact of Grapevine Leafroll Disease (GLD) using sprayable nanoparticles encapsulating computationally designed siRNA to match the virus's genome, thus helping thousands of winegrowers around the globe.
At a different project, we load agricultural nutrients into 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, thus recover tomatoes from acute nutrient deficiency which was not treatable using ordinary agricultural nutrients.
Robotics and Automation
Automated approaches and robotics are currently gaining traction in modern laboratories and facilities. This possesses key potential in shaping the future of science and research. Our laboratory innovates in the field of nanoparticle engineering by combining skills of computation and experimentation, in order to obtain a broader window of results and a more efficient workflow. Nowadays, multiple projects attempt to implement robotics as a part of research by learning computational software and basic programming. In addition, since robotic devices are programmed using an adjacent terminal, it means that they can be accessed remotely. For this reason, numerous laboratories that lack the resources or machinery to perform complex experimentation are able to request access to our labware. Moreover, we developed an academic course centered in the use of robotics in nanotechnology aimed at high school and university students, which even further contributes to the idea of remote experimentation. Ultimately, the strive to create an AI system, which will revolutionize the process of nanoparticle engineering and analysis to improve the field of personalized medicine and targeted drug delivery is one of our key goals and ambitions.
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.
A time-lapse movie of the morphological change of fibroblasts following collagen fiber relaxation with collagenase
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.
Specifically, We design Liposomes that interfere with primary metabolic processes of the tumor microenvironment, including acidification, by delivering alkaline buffers to the tumor.
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.
Specifically, nanotechnologies that are targeted simultaneously to multiple metastatic sites in the body while carrying small-molecule drugs, proteins, nucleic acids or imaging agents, will enable management of metastatic cancer.
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.
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.