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 are artificial systems capable of replacing malfunctioning cells inside the body. 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.
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 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.
Specifically, We design Liposomes that interfere with primary metabolic processes of the tumor microenvironment, including acidification, by delivering alkaline buffers to the tumor.
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
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.
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.