Single Walled Carbon Nanohorns as Photothermal Absorbers, and Incorporation of Spatial Digital Image Analysis into Cancer Diagnostics and Therapy

Abstract

Background: Photothermal therapy is an actively researched cancer treatment alternative to chemotherapy and resection due to its potential as a minimally invasive treatment with fewer health complications than high energy radiation therapies. The effectiveness of photothermal therapy may be enhanced with the use of photoabsorbtive nanoparticles by increasing heat generation and improving spatial selectivity. While photothermal therapy is a spatially distributed treatment, traditional experimental analysis methods used to assess photothermal therapy have either lacked spatial assessment such as is the case with standard viability assays of cell monolayers, or they only provide macroscopic treatment information, such as the measurement of the diameters of implanted mice flank tumors post-treatment.

Goals: This work aims to accomplish two major goals. The first is to determine the therapeutic impact of combining Single Walled Carbon Nanohorns (SWNHs) with photothermal therapy. The second is to advance the measurement tools used to assess photothermal therapy by developing viability measurement methods which incorporate detailed quantitative spatial information

Methods: Photothermal therapy was tested with and without SWNHs in in vitro cell monolayers, in vitro tissue phantoms, and ex-vivo tissue. Digital image analysis methods were developed which allowed for the use of viability assays and histological information to be identified and organized spatially. These methods were then used to compare the impact of cellular microenvironment and heating method on Arrhenius parameters.

Results: The inclusion of SWNHs dramatically increased the temperatures reached in each experiment. Digital image analysis methods were shown to quantify spatial viability with a high degree of accuracy and precision in 2D and 3D. Experimental data indicated that there were areas of collateral damage (partially treated tissue) surrounding areas of completely treated tissue ranging which were between 46% and 78% of the completely treated volume. In each case the heat transfer properties of the experimental system had a large impact on the area of treatment. Variation in the temperature and viability response of photothermal therapy for specific laser and nanoparticle treatment parameters was quantified.

Conclusions: This research has brought an experimental cancer treatment procedure from experiments in cell monolayers to tests in ex-vivo tissue to analyze viability response. The strengths of photothermal therapy such as its minimally invasive nature, and effectiveness at killing cells were experimentally demonstrated. This research has also developed the tools necessary to assess the spatial impact in vitro and lay the foundations for assessing spatial impact in vivo. These tools may be used to assess other treatments beyond photothermal therapy, and serve as a basis for improving the analysis of biological systems both in vitro and in vivo.