University of Arkansas for Medical Sciences,
Keywords: nanotesting, cancer, nanotechnology, blood
Summary:Cardiovascular diseases, cancers, and infections remain the main causes of death in the U.S. and worldwide. The diagnosis of many diseases begins with a common medical procedure: examination of extracted blood samples. The sensitivity of current blood test is limited by the small volume of blood collected, in which no less than one disease-specific marker (e.g., tumor cell, clot, virus and bacterium) can be detected. This method can miss many thousands of abnormal cells in the whole blood volume (~5 liter in adults), which can be sufficient for disease progression to difficult-to-treat if not already incurable complications (e.g., metastasis, stroke, or sepsis). We have developed novel concept of early disease diagnosis (“in vivo reading written in blood”) by in vivo photoacoustic (PA) detection of disease-associated circulating markers using both natural (e.g., melanin in melanoma and hemozoins in malaria) or artificial functionalized nanoparticles as high contrast PA agents. Unlike typical blood sampling involving extraction of a volume of blood ranging from 10 µL (one drop) to a few milliliters, in vivo examination involves nearly the entire volume of blood passing through 1–2-mm-diameter peripheral vessels over 0.5–1 h (a few minutes in larger vessels) and thus will enable a dramatic increase in diagnostic sensitivity, ultimately up to 103–105 times, reflecting the ratio of the volume of blood sampled in vivo to that in vitro. In addition, the integration of simultaneous diagnosis and therapy—theranostics—can eradicate circulating abnormal cells, and thus can potentially prevent, or at least inhibit deadly metastasis, sepsis or stroke. This report summarizes recent advances of this platform with focus on multiplex nano-theranostics of melanoma, malaria, S. aureus –related sepsis, and thrombosis. First clinical applications of this technology for preventions of metastasis and stroke are discussed.