Lasers and nanomaterials are two of the most significant technological advances of the 20th century. The combination of lasers and nanotechnology holds great promise in the fields of biology and medicine. The long- term objective of this project is to develop a multifunctional bionanoprobe for targeted drug delivery, tumor imaging, and photoimmunotherapy for metastatic cancers. The PIs plan to use a novel method (patent pending) to construct a stable solution of single-walled carbon nanotube (SWNT) using a highly potent immunostimulant, glycated chitosan (GC), as an effective surfactant. In this project, the PIs plan to construct, simulate, and calibrate this bionanoprobe, determine its physical and biological characteristics, study its interactions with normal and tumor cells, investigate its toxicity, and determine its photoimmunological effects for treatment of metastatic tumors both in vitro and in vivo. We assume that this bionanoprobe can carry different molecules into tumor cells. We further hypothesize that this novel bionanoprobe, when localized inside tumor cells and combined with laser irradiation of appropriate wavelengths, can induce temporally and spatially synchronized photothermal and immunological reactions for treatment of metastatic cancers. The novelty of this bionanoprobe lies in the unique molecular structures of SWNT and GC so that a strong non- covalent bond can be formed for a stable nanotube solution. Furthermore, selective photothermal interaction can be achieved using in situ SWNT-GC with an absorption peak in the near-infrared region. This ensures a synchronized spatial and temporal thermo-biological effect in target tissue during non-invasive laser irradiation. In this project, the PIs will modify the bionanoprobe with fluorescent molecules to study its cellular distribution and to explore its capability to carry different peptides and therapeutic agents into tumor cells. The PIs will also use magnetic resonance thermometry to determine real-time, 3-dimensional temperature distributions in target tumor tissue during laser irradiation, which could help establish a correlation between temperature increases in tumor tissue and induced immunological responses. Specifically, the PIs plan to achieve the following aims: (1) To construct, calibrate, simulate, investigate, and modify the multifunctional bionanoprobe; (2) To investigate the cellular effects of the multifunctional bionanoprobe; and (3) To determine in vivo efficacy of laser-SWNT-GC for treatment of metastatic cancers. Successful completion of this project will pave the way to future explore the potential applications of this novel multifunctional bionanoprobe in biology and medicine, particularly in cancer treatment.

R21EB015509

2013-08-01

2016-07-31