Efficient preparation of highly pure chlorin e6 and its photodynamic anti-cancer activity in a rat tumor model

Abstract

Abstract. Photodynamic therapy (PDT) is currently being used as an alternative therapeutic modality for a variety of malignant tumors. This study was performed to show an efficient preparation of second generation of photosensitizer chlorin e 6 (Ce 6 ) with high yield and purity, and to test antitumor activity of Ce 6 -induced PDT (Ce 6 -PDT) both in vitro and in vivo using a rat tumor model. Three-week-old male Sprague-Dawley (SD) rats were inoculated s.c. on the right flank with 5x10 6 RK3E-ras cells. The animals were administered i.v. with Ce 6 (10 mg/kg) and 24 h later, PDT was performed using a laser diode at a light dose of 100 J/cm 2 . Ce 6 -PDT generated reactive oxygen species and led to significant growth inhibition in RK3E-ras cell. In addition, Ce 6 -PDT induced apoptosis through the activation of caspase-3 and its downstream target, PARP cleavage. The protein level of antiapoptotic bcl-2 was also reduced by Ce 6 -PDT in RK3E-ras cells. In in vivo experiments, application of Ce 6 -PDT led to a significant reduction of tumor size. PCNA immunostaining and TUNEL assay revealed that Ce 6 -PDT inhibited tumor cell proliferation and increased apoptosis. These findings suggest that the newly purified Ce 6 -PDT can effectively arrest tumor growth by inhibiting cell proliferation and inducing apoptosis.

Enhanced tumor localization and retention of chlorin e6 in cationic nanolipoplexes potentiate the tumor ablation effects of photodynamic therapy

“…We observed the formation of thick scabs on the tumor sites after the systemic administration of liposomal Ce6 at a dose of 2.5 mg kg −1 , a dose of free Ce6 that did not exert any antitumor effects. In a previous study, Ce6 was systemically administered in free form, and its in vivo photodynamic anticancer activity manifested at a dose of 10 mg kg −1 , four times higher than our liposomal Ce6 dose [27]. The therapeutic efficacy of nanocomplexed Ce6 at a much lower dose supports the idea that the potency and required dosage of Ce6 can be modulated by designing appropriate nanolipoplexes.…”

Novel Broad-Spectrum Antimicrobial Photoinactivation of In Situ Oral Biofilms by Visible Light plus Water-Filtered Infrared A

“…As a result, the partition coefficient P and thereby its lipophilicity increase with declining pH values, leading to a higher Ce6 uptake by nonspecific lipoprotein targets on the bacterial membrane, especially in the presence of infrared radiation (69). The long-lasting photoexcited triplet state of Ce6 can also be considered a favorable photophysical feature of this plant-derived photosensitizer (68,70). Interestingly, Ce6 also showed affinity for human serum albumin and low-density lipoproteins (LDL) (71).…”

“…Ce6 is a chlorophyll a-based second-generation photosensitizing agent, which is derived from the green seawater alga Chlorella (Chlorella ellipsoidea) (67). Except for the fractional saturation of a pyrrole ring, its structural resemblance to porphyrins is responsible for the varying, pH-dependent charge of the molecule (68). As a result, the partition coefficient P and thereby its lipophilicity increase with declining pH values, leading to a higher Ce6 uptake by nonspecific lipoprotein targets on the bacterial membrane, especially in the presence of infrared radiation (69).…”

Investigation of artificial cells containing the Par system for bacterial plasmid segregation and inheritance mimicry

“…1 ). Ce6 is a commonly used photosensitizer that is isolated from Chlorella ellipsoidea 41 . Reactive oxygen species are produced by Ce6 under laser (405 nm) irradiation (Supplementary Fig.…”