Abstract B151: Monitoring tumor microenvironment (Hb saturation and oxygenation) in response to plasmonics-assisted photothermal cancer therapy.

Introduction: Advanced biophotonic technology provides a novel strategy to not only achieve target-specific cancer therapy, but also monitor physiological response during treatment. To date, photoactivatable plasmonic nanoparticles (e.g. nanostars; NS) have been applied for region-controlled photothermal, photodynamic, and photoimmuno therapy. Environmental sensitive nanoparticles (e.g. boron nanoparticles; BNP) also can be utilized for oxygen sensing through optical imaging and spectroscopy. However, very little is understood on the physiological impact of these nanoparticles following photon activation, especially on live animals. Methods: We employed syngeneic tumor animal models implanted in dorsal window chambers to study the local partial pressure of oxygen (pO2) and Hb oxygen saturation (HbSat) changes following plasmonics-assisted photothermal therapy (PTT). Near IR (NIR) responsive PEGylated plasmonic gold nanostars (PEGNS) or saline controls were injected intravenously to mice pre-implanted with Lewis Lung cancer cells in the dorsal window skin chambers. BNP were locally injected into the chamber for oxygen sensing. On each mouse (PEGNS vs. control), following 10 minutes of low-energy (0.5 W/cm2) or high-energy (1 W/cm2) irradiation of 785 nm laser. Series of images were collected via hyperspectral microscopy to assess pO2 and HbSat for 4 days. Results: Chemical characterization of PEGNS showed a hydrodynamic size of 50-nm and an extinction maximum around 800 nm. BNP has a hydrodynamic size of 90-nm and extinction maximum around 420 nm. Pre-PTT microscopy imaging showed the presence of tumor cells and neovascularization 8 days following cancer cells implantation. PEGNS were seen in perivascular space and scattered throughout the skinfold 1 day following injection. pO2 and HbSat were monitored successfully using optical methods. Mice receiving PTT with PEGNS showed apparent tumor ablation and hemorrhage on high-energy PTT but only small hemorrhage on low-energy PTT. High-energy PTT damaged the blood vessels causing subsequent tissue scarring formation and low pO2/HbSat profiles. Low-energy PTT induced small vascular damage; focal elevation of pO2/HbSat surrounding the tumor vessels was found on day 4. Mice receiving PTT without PEGNS displayed no hemorrhage but only mild skin redness after high-energy irradiation. Irradiation may lead to photon energy-dependent inflammation without damaging blood vessels. Tumor periphery vascular growth with elevated pO2 and HbSat were apparent. Conclusion: In this pilot study, we for the first time demonstrated the potential of using NS and BNP combined with optical imaging/spectroscopy technologies to investigate the tumor microenvironment in response to two different energy levels of PTT or irradiation alone. Successful PTT may not only ablate the tumor tissue/vessels but also reduce the local pO2 and HbSat. In contrast, irradiation alone may induce local inflammation hence elevated pO2 and HbSat. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):B151. Citation Format: Hsiangkuo Yuan, Christina L. Hofmann, Jelena Samonina-Kosicka, Hansford Hendargo, Gabi Hanna, Tuan Vo-Dinh, Cassandra L. Fraser, Mark W. Dewhirst, Gregory M. Palmer. Monitoring tumor microenvironment (Hb saturation and oxygenation) in response to plasmonics-assisted photothermal cancer therapy. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr B151.