A leucine aminopeptidase activatable photosensitizer for cancer cell selective photodynamic therapy action. (November 2021)

• Record Type: Journal Article
• Authors: Arslan, Busra; Bilici, Kubra; Demirci, Gozde; Almammadov, Toghrul; Khan, Minahil; Sennaroglu, Alphan; Acar, Havva Yagci; Kolemen, Safacan
• Is Part Of: Dyes and pigments. Volume 195(2021)
• Publication Date: 2021-11
• Subjects: Cancer -- Photodynamic therapy -- Leucine aminopeptidase -- Hemicyanine -- Activity-based photosensitizers; Dyes and dyeing -- Periodicals; Pigments -- Periodicals; 667.2
• DOI: 10.1016/j.dyepig.2021.109735
• Languages: English
• ISSNs: 0143-7208

Abstract

Abstract: Activity based photosensitizers (PS) continue to attract great attention as they enable selective photodynamic therapy action on cancer cells while sparing normal cells even under light irradiation. Sensitivity to specific enzymes that are differentially overexpressed in cancer cells is crucial in the design of activatable PSs. In this direction, we report here, for the first time, a leucine aminopeptidase (LAP) activatable PDT agent (HCL ), which is a red-shifted, water soluble and photostable brominated hemicyanine derivative. HCL was activated by endogenous LAP enzyme selectively in A549 (lung) and HCT116 (colon) cancer cells containing high LAP levels and induced effective photocytotoxicity with negligible dark toxicity. Furthermore, the fluorescence of the parent bromo-hemicyanine core was restored upon LAP-based activation in cancer cells. On the other side, no remarkable phototoxicity or fluorescence turn-on was detected in healthy L929 cells. Thus, HCL serves as an effective and tumour associated LAP-sensitive phototheranostic agent. We believe different cancer-associated analytes can be utilized in combination with near-IR absorbing scaffolds in the scope of activatable PDT designs to enrich the tumour-selective PS arsenal. Graphical abstract: Image 1 Highlights: A leucine aminopeptidase (LAP) responsive phototheranostic agent (HCL) was developed. HCL marks the first ever example of a LAP activatable photodynamic therapy (PDT) agent. HCL exhibited red shifted absorption and emission signals upon activation. Selective photocytotoxicity and turn-on fluorescence response on cancerous A549 and HCT-116 cells were detected. No activity was observed in normal L929 cells.