Improved Pilot-Plant-Scale Synthesis of Chlorin e6 and Its Efficacy as a Photosensitizer for Photodynamic Therapy and Photoacoustic Contrast Agent

Abstract

Photodynamic therapy and photoacoustic (PA) imaging are emerging therapeutic modalities for the diagnosis and treatment of various types of cancer or other diseases. In this study, the second-generation photosensitizer Chlorin e6 was prepared on a pilot scale by using the rapid, simple, and green synthetic method as compared to a conventional protocol. In the modified method, the extraction/reaction time and volume of solvents were significantly reduced. The dark and photodynamic cytotoxicity of Ce6 was measured against B16F10 melanoma cell line. Ce6 did not affect cancer cells in the dark up to 192 µM, ensuring their safety in the absence of light. After PDT, it displayed significant cytotoxicity at lower concentrations (IC50: 18.9 µM). For in vivo study, B16F10 allograft mice were treated with Ce6 at 2.5 mg/kg and then exposed to red light (660 nm) after 3 h. The Ce6-PDT caused the inhibition of tumor growth. Furthermore, Ce6 was also used as a photoacoustic imaging agent in ICR mice to visualize the internal organs. Therefore, this study provides valuable information about Ce6-PDT as a promising strategy for anti-cancer therapy as well as visualization of internal organs without surgery or x-rays.