This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Nanotechnology holds great promise for the treatment of diseases like cancer. In this regard, gold nanoparticles (AuNPs) have biomedical applications such as drug delivery, imaging, and hyperthermic tumor cell ablation. Cancer targeted therapies rely on exploiting susceptibility parameters of tumor versus normal cells. The increased susceptibility of tumors to heat makes hyperthermia a feasible treatment option. A variety of heat sources have been explored, including laser light, focused ultrasound, as well as microwaves. More recently, the use of near infrared-absorbing gold nanoparticles has successfully been applied to reduce tumor burden and increase survival in animal experiments. Selectivity of heat induction is based on enhanced permeability of the tumor vasculature and subsequent retention of the intravenously administered nanoparticles, which can be heated using deep penetrating near infrared (NIR) laser light. However, enhanced permeability and retention pathophysiology does not occur in all tumors, mandating alternative methods of targeted nanoparticle tumor delivery before successful clinical application can be achieved. Lack of AuNP targeting to tumor cells is a major impediment for realization of these therapeutic possibilities. Therefore, we propose to use targeted adenoviral (Ad) gene therapy vector as a platform for selective assembly and specific delivery of AuNPs to tumors. This would also allow a combination of gene therapy and nanotechnology for the treatment of cancer. We have previously demonstrated that AuNPs can be non-specifically coupled to Ad vectors. We herein aim to further this paradigm by coupling AuNPs to specific Ad capsid locations and thus avoiding the detrimental effects on Ad infectivity and targeting that were observed with the non-specific approach. This type of combinatorial system represents a novel paradigm for the design of tumor-targeted nanoparticles. Dr. Perkins (NCMIR) is aiding the effort to visualize the number and distribution of the gold nanoparticles (AuNPs) on the virions.
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