Engineered near-infrared nanomaterials for cancer theranostics: Integration of photophysical components

Engineered nanomaterials hold great promise for the development of next generation nanomedicine, such as image-guided-therapy, early-stage-detection and therapeutic monitoring of diseases. Current research efforts are focused on the development and application of these nanomaterials for cancer treatment. The ultimate goal in this research field is to develop multifunctional nanoparticles (MNPs) that can specifically locate and selectively destroy cancer cells. The focus of present studies was on the development of engineered MNPs to overcome the limitations associated with mono-functional imaging and therapeutic agents. The MNPs were strategically engineered by integrating photophysical components such as flurophores for optical imaging and photothermal materials for ablative therapy.;Molecular assembly of organic fluorophores was controlled inside an inorganic matrix to attain hybrid nanoparticles with enhanced optical properties. The high detection sensitivity of these near-infrared fluorescent (NIRF) nanoparticles (size 40nm) was demonstrated in vivo by fluorescence imaging at 10 time lower concentration than quantum dots. Surface modification strategies, involving functionalization of NPs (utilizing biotin-avidin chemistry) with small tumor targeting proteins, were employed to deliver these nanoparticles to uniquely identified sites in tumor environment with ∼10% efficiency.;Subsequently, these NIRF nanoparticles were modified to exhibit photothermal properties by integration of either photothermal materials within the NIRF particulate structure. Conventionally used plasmonic photothermal materials due to their size and shape restrictions could not be incorporated in the NIRF nanoparticles. A novel strategy based on interplasmon coupling between sub 4nm gold nanoparticles was developed to overcome this limitation. Surface of NIRF NPs was decorated either externally or internally with small gold nanoparticles in a controlled fashion (surface coverage 6-14%, size 0.7, 1.2, and 3.8nm). The gold speckled silica nanoparticles thus formed exhibited both optical luminescence and photothermal properties. Another strategy to incorporate photothemal properties in NIRF NPs was based on mixed micelles mediated synthesis of organic-inorganic hybrid structures. Molecular photothermal agents such as metal-naphthalocyanine dyes were incorporated inside the pores of NIRF NPs (photothermal: fluorescence dye 4:1). The high optical absorbance cross-section and optical imaging properties of MNPs were utilized for image guided photothermal ablation (tumor necrosis > 90%) of a human breast cancer tumor inside mice.