Low dose hypericin-PDT induces complete tumor regression in BALB/c mice bearing CT26 colon carcinoma

Summary 

Background

Successful tumor eradication with photodynamic therapy (PDT) in vivo depends on the optimal combination of treatment parameters. (Low-dose) PDT may additionally induce antitumoral immune responses. Since the naturally occurring hypericin (Hyp) is a promising photosensitizer for PDT, the aim of the study was to investigate phototoxic and immunologic effects of a low-dose Hyp-PDT on murine tumors in contrast to commonly used Hyp-PDT conditions.

Methods

BALB/c mice bearing CT26 colon carcinoma received hypericin intravenously and were irradiated with red light 0.5–4h later. Tumor development was recorded. Mice were then re-challenged 60 days after the first tumor cell inoculation to investigate an antitumoral immune response.

Results

Different results of tumor/host responses were obtained, ranging from mice exitus over delayed tumor growth to complete tumor regression according to different treatment protocols. PDT with common doses and a 4h drug–light-interval resulted in a four times delayed tumor growth compared to the control groups. PDT with relatively low doses and a drug–light-interval of 0.5h led to 100% tumor eradication. Re-challenge of these mice with CT26 mouse colon carcinoma cells prevented new tumor growth.

Conclusions

Not only drug concentrations and light doses seem to determine the efficiency of tumor eradication, but also the localization of hypericin at the time of irradiation. Targets in our low-dose PDT protocol are exclusively the vessels. The advantage of this low-dose PDT beside less drug and light exposure of the animals is reduced skin damage, faster healing of the lesions and induction of an antitumoral immune response.

Keywords: Low-dose photodynamic therapy, Hypericin, BALB/c mice bearing CT26, Vascular damage, Antitumoral immune response