Injectable NanoVectors for Directed (Targeted/ Personalized) Therapy
The Need: Cancer is a major public health problem in developed countries, accounting for nearly one-fourth of deaths in the United States, exceeded only by heart diseases. According to a 2008 report by the American Cancer Society, estimated numbers for US cancer cases are 745 and 692 thousands for men and women, respectively, with the lifetime probability of developing cancer higher in men (45%) than in women (38%). Despite extraordinary progress in the laboratory research, cancer mortality has not been reduced by any significant amount in the last fifty years. The main reasons are that 'cancer' is actually not a single condition, but rather a general term, defining several hundreds of various diseases, which has in common uncontrolled division of cells, but differ dramatically in terms of their biology and response to therapy. Like malignant snow-flakes, no two cancers are identical, if one looks closely enough. Furthermore, very different metastatic colonies will evolve from the same primary cancer in a patient, leading to the impossibility of treatment with a sole drugs combination. Finally, upstream from the problem of successful recognition of molecular targets for therapeutic agents, is the need to achieve the efficient concentration of the drug at the target cancer tissue. The last is decoupled from intrinsic biological recognition but rather encounters for the different distribution of the drug in the human body as a result of intrinsic differences in the biology of the individuals and their disease. This happens because the body contains numerous 'traps' (biobarriers) that severely limit the penetration substances such as drugs into the different body organs and cancer tissue, limiting the efficiency of the medication. The quadruple problem of identifying different molecular targets, avoiding all biobarriers, delivering one or more cancer cell killing entities, and personalizing therapy has historically been addressed by trying to endow individual drug molecules for each of the above tasks or with all of these capabilities. This strategy has met with limited success.
Our Approach: We believe that nanotechnology offers unprecedented opportunities to develop treatments that increase therapeutic efficacy, decrease undesired side effects, and effectively achieve the personalization of intervention. The fundamentally novel approach is the decoupling of the quadruple functions through the use of 'carrier' particles ("NanoVectors") that possess sufficient multi-functionality to avoid biological barriers and recognize their targets. Their payload comprises simple cell killing agents (FDA-approved, possibly generic drugs), which are released at the desired site of intervention or contrast agents for efficient disease diagnosis and for monitoring of cancer progression and regression due to the therapy. In our laboratories we employ Multi-Stage NanoVectors to reach these objectives.
State of Development: We have developed the fundamental Multi-Stage NanoVector technology, and are in the process of validating it in-vitro and in-vivo in animal models of various cancers, including breast, ovaries, colon, pancreas and others. We are developing the mathematical tools for the selection from a combinatorial NanoVector library of the proper NanoVector therapy for individualized therapy. We have recently published our first findings about the Multi-Stage NanoVectors in such high-impact journals as Nature Nanotechnology and Biomaterials. We are keeping below radar on this line of research, and are planning to continue publishing on the topic in high-visibility scientific journals.
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A schematic presentation of Multistage delivery system mechanism of action (A) A non-toxic, biodegradable first stage carrier is optimally designed to evade reticulo-endothelial system and have margination, adhesion, internalization properties to attain preferential concentration on the target tumor blood vessels (B) The first-stage porous silicon particle co-releases second-stage carrier nanoparticles, with agents that facilitate its permeation through the tumor blood vessel wall into the tumor tissue. (C) The second stage nanoparticles penetrate the cellular membrane, and deploy different, synergistic therapeutic agents in the cytoplasm, the nucleus, or other targets inside the cell.
