The recent invention in our laboratories of 20-200 nm diameter optical nanosensors presents the opportunity for the development of a new class of drug delivery devices for non-invasive imaging using magnetic imaging resonance, and simultaneous delivery of therapeutic agents to brain tumors. These nano-devices can be passive or active modular entities capable of sensing the physiological environment or reporting the presence of a tumor. This proposal represents the first application of our nano-devices for investigating the delivery of these devices to experimental intracranial tumors. The hypothesis that nano-scale MR image contrast agents can be synthesized, delivered and imaged using MRI in experimental brain tumors will be tested by the following specific aims:
Specific Aim 1 (i) Synthesis and in vitro testing of encapsulated gadolinium contrast agent (Magnevist). (ii) Synthesis and in vitro testing of encapsulated MION contrast agent.
Specific Aim 2 A (i) In vivo evaluation of nanoparticle-encapsulated Magnevist (GdPEBBLEs) following single dose administration to assess dose and time course dependent-changes to intracerebral 9L tumor delivery. (ii) In vivo testing of GdPEBBLES following a multi-dosage schedule to evaluate maximal brain tumor uptake.
Specific Aim 2 B As in Specific Aim 2A, in vivo testing of MION PEBBLEs will be accomplished. Preliminary data collected by our group confirms the utility of MION for MRI of brain tumors. We propose incorporation of MION or gadolinium into the core of hydrogel nanoparticles for enhancement of contrast characteristics and quantification of delivery of DNP's to 9L brain tumors in rats. It is anticipated that the results from the proposed studies will provide the foundation for furthering the development of these novel nano-structure-based strategies for the imaging, characterization and simultaneous destruction of intracranial tumors.
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