Real-time vascular imaging and photodynamic therapy efficacy with micelle-nanocarrier delivery of chlorin e6 to the microenvironment of melanoma

Abstract

Background: Strategies combining anti-vascular therapy and vascular imaging may facilitate the prediction of early response and outcome in cancer treatment.

Objective: The aim of this study was to investigate the relationship between the tumor-associated vasculature in melanoma and to develop an approach for melanoma treatment by utilizing the free form and micelle form of the photosensitizer (PS) chlorin e6 in photodynamic therapy (PDT).

Methods: Green fluorescence protein (GFP) expressing B16-F10 melanoma cells were implanted into the mouse ear dermis. Ce6 in free form or in micelle form was administered via the tail vein. An OV100 imaging system was used to record the red fluorescence of Ce6 to obtain real-time vascular images in the GFP tumor.

Results: Compared to free Ce6, Ce6 linked to the micelle-nanocarrier depicted a much clearer vascular image and had an effective vascular destruction by PDT. Micelle Ce6 was localized in lysosomes and in the endoplasmic reticulum of cultured endothelial cells, implying an active endocytosis of the nano-carrier.

Conclusion: Micelle Ce6 can serve as a bifunctional PS for vascular imaging and PDT, which facilitates its delivery in the tumor microenvironment.

Keywords: Chlorin e6; Endothelial cells; Melanoma; Micelle; Photodynamic therapy; Tumor microenvironment.