AVS2014 Session BP+BI+AS-SuA: Biomaterials Plenary Session

We have employed Imaging MS in studies of a variety of biologically and medically relevant research projects. One area of special interest is the molecular mapping of changes observed in diabetes in both a mouse model and in the human disease. Major molecular alterations have been recorded in advanced diabetic nephropathy. Other applications include developmental studies of embryo implantation is mouse, renal cancers as well as that in other organs, and neurodegenerative disease. Molecular signatures have been identified that are differentially expressed in diseased tissue compared to normal tissue and also in differentiating different stages of disease. These signatures typically consist of 10-20 or more different proteins and peptides, each identified using classical proteomics methods. In addition, Imaging MS has been applied to drug targeting and metabolic studies both in specific organs and also in intact whole animal sections following drug administration.

This presentation will focus on recent technological advances both in sample preparation and instrumental performance to achieve images at high spatial resolution (1-10 microns) and at high speeds so that a typical sample tissue once prepared can be imaged in just a few minutes. Finally, new biocomputational approaches will be discussed that deals with the high data dimensionality of Imaging MS and our implementation of ‘image fusion’ in terms of predictive integration of MS images with microscopy and other imaging modalities.

The advent of novel engineering technologies affords unprecedented advances toward long-elusive objectives of medical research. Individualized medicine responds to the basic but generally unattainable questions of diagnosing a pathology at its earliest stage, when therapy is most effective, identifying the right therapy, reaching the right therapeutic target in the body at the right time, and securing immediate feedback as for its efficacy and undesired collateral effect. Individualized medicine appears to be a credible general objective in cancer and other fields of medicine, owing to the integration of classical disciplines of clinical medicine, methods of molecular biology, and novel technology platforms.

Nanotechnologies are of great interest in the context of the drive toward individualized medicine, and may prove to be the necessary catalyst for its large-scale implementation. In this talk I will present several nanoporous-silicon-based approaches for triple-negative breast cancer (TNBC). First, nano-textured chips for proteomic and peptidomic content profiling of biological fluid samples will be demonstrated for the identification of new biomarkers of TNBC. Second, employing methods of Transport Oncophysics, multistage vectors (MSV) will be shown to afford unprecedented therapeutic results in animal models of TNBC with pulmonary metastases, and to allow the in-vivo verification of novel hypotheses about the fundamental driver mechanisms for TNBC. Methods will also be shown to deliver combination therapeutics in exactly the same optimal proportions in vivo as their preparation in the laboratory. Thirdly, a nanochannel implant will be demonstrated, for the long-term release of agents for the prevention of local recurrences of TNBC, with a reduction of the concurrent loss of bone density.

It is hoped that these innovations will contribute to the fight against TNBC, which encompass multiple varieties of breast cancer, including those that arise from BRCA mutations, and which share the unfortunate reality of being associated with much poorer prognosis that the breast cancers that are responsive to estrogen therapy or Herceptin.