title: Combined concurrent photodynamic and gold nanoshell loaded macrophage-mediated photothermal therapies: an in vitro study on squamous cell head and neck carcinoma.
abstract: 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.
  
  
  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.
authors.affiliation: Beckman Laser Institute and Medical Clinic, University of California, Irvine, California, 92612.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Trinidad
authors.forename: Seok Jin
authors.initials: SJ
authors.lastname: Hong
authors.forename: Qian
authors.initials: Q
authors.lastname: Peng
authors.forename: Steen J
authors.initials: SJ
authors.lastname: Madsen
authors.forename: Henry
authors.initials: H
authors.lastname: Hirschberg
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000628:therapy*; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D016503:Drug Delivery Systems / Q000379:methods*; D006046:Gold / Q000627:therapeutic use*; D006258:Head and Neck Neoplasms / Q000628:therapy*; D006801:Humans; D006979:Hyperthermia, Induced / Q000379:methods*; D007211:Indoles / Q000627:therapeutic use; D008264:Macrophages; D057145:Nanoshells / Q000627:therapeutic use*; D009942:Organometallic Compounds / Q000627:therapeutic use; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000627:therapeutic use; D051381:Rats; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D009942:Organometallic Compounds; D017319:Photosensitizing Agents; C064331:aluminum phthalocyanine disulfonate; D006046:Gold
keywords: HNSCC; PDT; PTT; combinatorial PDT & PTT; gold nanoshells; hyperthermia; macrophage; photodynamic therapy; photothermal therapy; squamous cell carcinoma