טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
M.Sc Thesis
M.Sc StudentYathreb Asaad
SubjectEngineered Nanomaterials and Supramolecular Assemblies
for Biomedical Applications
DepartmentDepartment of Biomedical Engineering
Supervisors Professor Emeritus Lotan Noah
Professor Weihs Daphne


Abstract

Recent advances in the field of biomaterials allow one to design and assembly molecular and supramolecular entities, capable to perform a multitude of tasks.  A field of endeavor that is most demanding for such capabilities is the fight against cancer. Cancer is a leading cause of death worldwide, accounting for 8.2 million casualties in 2012. Deaths from cancer worldwide are projected to continue rising.

Metastasis, a process whereby cancer cells spread from the site of the original tumor to one or more other places in the body, is the most significant challenge to management of cancer as it accounts for 90% of cancer related-deaths. Current procedures aimed at eradicating solid tumors and their metastases are rather non-specific. These procedures substantially affect normal cells causing serious physical side effects. As such, different principles and novel therapeutic modalities are required, that will allow drugs to be targeted more specifically to the desired site of action.

ADEPT is the acronym for Antibody Directed Enzyme Prodrug Therapy. As the name suggests, it is a theranostic (combination of therapy and diagnostic) entity that selectively targets cancer cells by monoclonal antibodies that link to tumor associated antigens and, in cooperation with an attached enzyme that activates an inactive precursor, prodrug, at the vicinity of a tumor and, hence, destroying the targeted cell. Highly specific monoclonal antibodies needed for implementing this approach requires sophisticated production processes leading to hefty price tag that can reach $100,000 per patient per year of medication.

In this study, a novel, autonomous and anti-cancer soluble system is hereby introduced. This system simultaneously enjoys dual properties of diagnostics and therapeutics. It specifically targets and destroys cancer cells and monitors the therapeutic response by visualizing tumor lesions in the body. The system contains multiple antibodies; each antibody is characterized by low specificity and low affinity to its epitope. Nevertheless, those antibodies cooperatively attach to the cancer cell, together exhibiting high specific docking similar to one highly specific antibody. Our system proposes an innovative idea of recyclability. The selection of low affinity antibodies allows the module to detach from the cell remains following its destruction. Hence, each module will be reused and available again to diagnose additional cancer cells, substantially reducing treatment costs.  In this study, we aimed at studying the preliminary stages in the preparation of a model system of the theranostic module and practicing the techniques, assays, and the engineering aspects involved in designing and constructing of such theranostic module. Furthermore, the theranostic module, at advanced stages, is aimed to interact with living cancer cells. As a preliminary step, silica-based artificial cell models are hereby proposed.  They are based on fumed silica particles and are intended for use only in the early stages of the pertinent research and development activities. They can provide convenient system to research biological interaction without the requirement for biological sophisticated systems.

We believe that this study pave the way into designing theranostic modules that preferentially attack cancer cells thus, overcoming problems related to drug’s selectivity and price.