Design and development of nanoparticles for imaging and x-ray induced photodynamic therapy
Wang, Geoffrey D. S.
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The development of nanomaterials and nanosystems for biomedical applications is an area of considerable current interest in chemistry, materials science, and medicine. The basic rationale is that nanometer-sized particles have unique optical, electronic, or magnetic properties that are not available from either discrete molecules or bulk solids. Also, nanosized structures or scaffolds are well suited for covalent attachment and/or noncovalent encapsulation of multiple diagnostic and therapeutic agents, leading to theranostic (both therapy and diagnostic) and related multi-modal systems. In this context, the primary objective of this dissertation was to design and develop innovative nanoparticles for cancer imaging and therapy. For optical and MRI cancer imaging, we have developed dual-modality inorganic/organic nanostructures by embedding gadolinium (a magnetic contrast agent) into fluorescent carbon dots or europium-doped metal-organic frameworks (MOF). These nanoparticle probes show excellent in-vivo stability, strong fluorescence emission and improved magnetic contrast, moreover the gadolinium carbon dots are small enough (about 12 nm in diameter) for rapid renal clearance. For cancer therapy, we have developed x-ray induced photodynamic nanoparticles by coating a nanoscintilator core with mesoporpous silica and photosensitizers. In comparison with traditional photodynamic therapy (PDT), the use of x-ray to activate photosensitizing drugs allows greater tissue penetration and photodynamic treatment of deeply buried tumors. Also, in-vivo therapeutic studies using orthotopic cancer models have shown that x-ray induced PDT is a combination of photodynamic therapy and radiotherapy that synergistically target the cellular membrane and cellular DNA. Taken together, these findings provide important insights into the design and development of multi-modal nanoparticles for cancer molecular imaging and targeted therapy.