Combined concurrent photodynamic and gold nanoshell loaded macrophage-mediated photothermal therapies: an in vitro study on squamous cell head and neck carcinoma.

BACKGROUND AND OBJECTIVE Treatment modalities, such as hyperthermia and photodynamic therapy (PDT) have been used in the treatment of a variety of head and neck squamous cell carcinoma (HNSCC), either alone or as an adjuvant therapy. Macrophages loaded with gold nanoshells, which convert near-infrared light to heat, can be used as transport vectors for photothermal hyperthermia of tumors. The purpose of this study was to investigate the effects of combined macrophage mediated photothermal therapy (PTT) and PDT on HNSCC cells. STUDY DESIGN/MATERIALS AND METHODS Gold nanoshell loaded rat macrophages either alone or combined with human FaDu squamous cells in hybrid monolayers were subjected to PTT, PDT, or a simultaneous combination of the two light treatments. Therapies were given concurrently employing two laser light sources of λ = 670 nm (PDT) and λ = 810 nm (PTT), respectively. RESULTS Significant uptake of gold nanospheres (AuNS) by rat alveolar macrophages was observed thus providing the rationale for their use as delivery vectors. Viability of the AuNS-loaded Ma was reduced to 35 and 12% of control values at an irradiance of 14 or 28 W/cm(2) administered over a 5 minute period respectively. No significant cytotoxicity was observed for empty Ma for similar PTT exposure. AlPcS2a mediated PDT at a fluence level of 0.25 J/cm(2) and PTT at 14 W/cm(2) irradiance had little effect on cell viability for the FaDu/Ma (ratio 2:1) hybrid monolayers. In contrast, combined treatment reduced the cell viability to less than 40% at these same laser power settings. CONCLUSIONS The results of this study provide proof of concept for the use of macrophages as a delivery vector of AuNS for photothermal enhancement of the effects of PDT on squamous cell carcinoma. A significant synergy was demonstrated with combined PDT and PTT compared to each modality applied separately.