In compromised vasculature and microvasculature systems, blood vessels may display increased leakiness through the blood vessel walls. Diseases where vasculature may be compromised may include cancer, stroke, aneurysm, and internal bleeding. The development of compositions and methods to identify leaky vasculature would be beneficial for early detection and for prognosis of such conditions. Currently, no adequate clinical tool exists to transparently and non-invasively identify and characterize leaky and compromised vasculature.
A related need exists for compositions and methods useful for patient specific, customized tumor characterization and therapy. Nano-systems exist for the diagnosis and treatment of many diseases, especially cancer. Nano-systems offer the possibility of multifunctionality and are being actively developed for in vivo imaging, biomolecular profiling of biomarkers, and targeted drug delivery. Such systems offer the potential to enhance the therapeutic index of anti-cancer agents, either by increasing the drug concentration in the tumor site, decreasing the exposure of healthy tissue, or both.
Most solid tumors require a complex microvasculature network for their growth. This blood microvessel network includes a dense immature blood vessel system with a high degree of tortuosity and increased leakiness through the vessel wall. The success of chemotherapeutic nano-agent therapy for solid tumors is dependent, at least in part, on the access that these agents have to tumors via the so-called leaky vasculature of the tumor. The development and effectiveness of the above described nano-systems is currently limited because no adequate clinical tool exists to transparently and non-invasively predetermine whether the blood vessels of the tumor may be amenable to nano-carrier-mediated therapy in an individualized, patient-specific manner—that is, to determine whether the tumor has a leaky vasculature.
Moreover, no adequate clinical tool exists for co-encapsulation of therapeutic or anticancer agents with non-radioactive contrast enhancing agent to allow for direct X-ray visualization of the biodistribution of the therapeutic or anticancer agents in the body of a subject.