Nanoconstructs For Targeting, Imaging, And Photothermal Therapy Of Cancer
Nanomaterials are becoming attractive for a variety of medical applications with over 250 nanotechnology-based products in U.S. pharmaceutical pipelines. Nanoparticle-based targeting has the potential to improve upon the limitations of conventional pharmaceuticals and increase the efficacy of drug delivery, therapy and imaging systems while reducing the side effects to healthy tissues. Due to the unique properties at nanometer scale, metallic nanomaterials have increasingly garnered interest as potential agents for selective molecular targeting, imaging, therapy, drug delivery and therapeutic applications. Research efforts that initially focused on rational design of passively delivered therapeutic system have recently progressed to the development of "second-generation" systems that can actively seek out cell markers and specific organs or cells based on over-expressed surface markers such as antigens expressed on cancer cells. This thesis reports on the development of second-generation targeted metallic-based therapy and diagnostic agents for potential heat-induced therapy and for magnetic resonancebased (MR) imaging. Here, we have developed selectively targeted metallic nanostructures that are conjugated to antibodies and have demonstrated their uses in molecular targeting, multimodal imaging, and in thermotherapy (photothermal therapy) applications both using in vitro as well as in animal models. Initially, we have synthesized and designed iron oxide-gold hybrid nanoparticles (HNPs) to make stabile water-soluble particles with suitable end functional groups that allow attachment of targeting antibodies. Next, the HNPs have been tested for cytotoxicity using targeted colorectal cancer cell lines. Further experiments were used to test the potential uses of these hybrid nanoparticles for dual functions for photothermal therapy as well as for MRI. On the basis of promising in vitro results, HNPs were tested in xenograft mice to illuminate the ability to achieve localized particle delivery following systemic injection. Particle localization was visualized by optimal fluorescence imaging and corroborated by non-invasive MR imaging and by histological tissue staining. After local particle delivery, effective photothermal therapy application has been demonstrated where tumor damage was observed posttreatment. Gold nanorods have become attractive for deep tissue in vivo photothermal therapy applications. We have demonstrated a novel method of coating with polyacrylate, resulting in stabile water-soluble nanorods. Further, the heating capacity of nanorods solution and selective in vitro photothermal therapy applications has been demonstrated.
Photothermal therapy; Imaging; Nanocontructs
Batt, Carl A
Estroff, Lara A.; Feigenson, Gerald W
Ph.D. of Biomedical Engineering
Doctor of Philosophy
dissertation or thesis