Macrophages as a photosensitizer delivery system for photodynamic therapy: Potential for the local treatment of resected glioblastoma

Abstract

Background: Photodynamic therapy (PDT) efficacy is determined in part by the concentration of photosensitizer (PS) at the treatment site. The blood-brain barrier (BBB) poses a significant limitation on the transport of PS into the post-operative resection region where brain tumors most often recur. Macrophages (Ma), as opposed to free or nanoparticle bound agents, are known to actively migrate to and around tumors, and can therefore be used as delivery vectors for both drugs and photosensitizers. Methods: Mouse Ma (RAW264.7) and F98 rat glioma cells were used in all experiments along with the photosensitizer AlPcS2a. Mitomycin-treated Ma were loaded with photosensitizer (PS) and mixed with glioma cells, forming hybrid spheroids. F98 spheroids were incubated with supernatants derived from PS-loaded Ma (MaPS). Light treatment (PDT) was administered at various radiant exposures from a 670 nm diode laser. The growth of both types of spheroids was evaluated by measurement of spheroid volume after 14 days in culture. Results: PDT on F98 cell spheroid cultures, mediated by either free or PS-released from Ma, demonstrated a significant growth inhibition with supernatants harvested after 4 and 24 h. A significant PDT-induced growth inhibition was demonstrated in the MaPS/F98 hybrid spheroid experiments. Conclusion: Since the efficacy of PDT, mediated by either free or released photosensitizer was comparable, the uptake and released photosensitizer was not degraded. MaPS, incorporated in hybrid tumor spheroids also mediated effective PDT. These results indicate that Ma have potential as an effective vector for photosensitizer delivery to resected brain tumors.

Keywords

• Photodynamic therapy
• Macrophage delivery
• Blood brain barrier
• Photosensitizer