Developing and evaluating therapeutic effect of a novel CB2 receptor-targeted photosensitizer in cancer

Objectives Phototherapy allows for direct injury to the locally irradiated tumor cells and tissues. Despite the recent advances in developing photosensitizers, current existing phototherapeutic agents lack tumor selectivity; therefore normal tissues can also be damaged, leading to considerable side effects. Here we report the first type 2 cannabinoid receptor (CB2R)-targeted phototherapy study using a novel phototherapy agent, IR700DX-mbc94.

Methods We synthesized a novel photosensitizer IR700DX-mbc94 based on a NIR phthalocyanine dye and a functional CB2R targeted molecule. To study the phototherapeutic effect of IR700DX-mbc94, we used CB2R+ and CB2R- mouse malignant astrocytoma cell lines. We evaluated in vitro therapeutic effect after treatment of IR700DX-mbc94 and NIR light irradiation. Furthermore, in vivo phototherapy study was conducted using subcutaneous tumor bearing mice.

Results We found that IR700DX-mbc94 caused significant phototoxicity when bound to the target receptor, suggesting a receptor-mediated therapy mechanism for phototherapy. In addition, IR700DX-mbc94 showed phototherapy effect in CB2R- cells at much less extent than in CB2R+ cells, indicating the target specific nature. Importantly, IR700DX-mbc94 showed promising photo therapeutic effect in vivo.

Conclusions We report the first type 2 cannabinoid receptor-targeted phototherapy study using a novel photosensitizer (IR700DX-mbc94) based on a NIR phthalocyanine dye and a functional CB2R-targeted molecule. IR700DX-mbc94 appears to have great potential in cancer phototherapy with high target selectivity, both in vitro and in vivo.