In vitro and in vivo evaluation of a chlorin-based photosensitizer KAE® for cancer treatment.

Background: Photodynamic therapy (PDT) has been approved for the clinical treatment of cancers. Photosensitizer (PS) is a crucial element of PDT. In the current study, in vitro and in vivo evaluation of a chlorin-based photosensitizer KAE® was performed.

Methods: The physicochemical characteristics of KAE® were compared with chlorin e6. The intracellular distribution of KAE® in HeLa cells was observed by laser scanning confocal microscopy. Reactive oxygen species (ROS) generation was detected through a 2', 7-dichlorodihydrofluorescein diacetate probe. The pharmacokinetics of KAE® was studied in mice. The photodynamic activities of KAE® and porphyrin based PSs were compared both in vitro and in vivo. The biosafety of KAE® in mice was evaluated by pathological section observation, blood routine examination and biochemistry assays.

Results: KAE® was readily dissolved in an aqueous solvent in a clinically acceptable concentration and showed a strong absorption at around 660 nm. Most of KAE® was located in the mitochondria of the tumor cells. Compared with hematoporphyrin derivative and 5-aminolevulinic acid, KAE® displayed a higher efficiency in cell killing. Furthermore, it could be completely eliminated from mouse body in 2 days. KAE® had no toxicity to mice under the tested dosage.

Conclusions: Our results suggested that KAE® is an effective and safe PS for PDT in cancer therapy and has a promising prospect for clinical application.