Tumor targeting chlorin e6 heptamethine cyanine conjugates: Theranostic agent for cancer imaging and photodynamic therapy.

Abstract

e15132 Background: Certain heptamethine cyanine dye derivatives like MHI-148 (1a) and IR-783 exhibit strong affinity for cancer cells. These dyes selectively target and accumulate within cancer cells due to overexpression of organic anion-transporting polypeptides (OATPs) and hypoxia-induced factors. In contrast, chlorin e6 (Ce6, 4), a commonly used photosensitizer in cancer treatment, lacks effective cancer targeting, leading to limited therapeutic efficacy and non-specific tissue damage. Methods: To enhance Ce6's tumor specificity, researchers developed novel tumor-targeting photosensitizer-carrier-conjugates (PSCs) by attaching Ce6 to heptamethine cyanine dyes. Results: These PSCs showed improved cancer cell uptake and retention compared to Ce6 alone, as demonstrated in breast cancer cells (MCF7) both in vitro and in mice xenograft models. The synthesis of PSCs involved three steps starting from Ce6 anhydride, yielding moderate results. The conjugates were complexed with either cold Cu for reference or radioactive 64Cu for quantitative studies and PET imaging. Both complexed and non-complexed PSCs were effective for in vitro and in vivo imaging studies. NIRF imaging revealed enhanced cancer cell uptake of PSCs compared to Ce6 alone, while PET imaging provided quantitative tumor visualization. PSCs demonstrated superior tumor imaging efficiency compared to 18F-FDG in mice xenografts. Conclusions: These findings highlight the potential of PSCs as multifunctional theranostic agents for image-guided photodynamic and radiotherapeutic cancer treatment.