A leucine aminopeptidase activatable photosensitizer for cancer cell selective photodynamic therapy action


Arslan B., Bilici K., Demirci G., Almammadov T., Khan M., Sennaroglu A., ...Daha Fazla

Dyes and Pigments, cilt.195, 2021 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 195
  • Basım Tarihi: 2021
  • Doi Numarası: 10.1016/j.dyepig.2021.109735
  • Dergi Adı: Dyes and Pigments
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Aerospace Database, Chemical Abstracts Core, Chimica, Communication Abstracts, Compendex, INSPEC, Metadex, Civil Engineering Abstracts
  • Anahtar Kelimeler: Cancer, Photodynamic therapy, Leucine aminopeptidase, Hemicyanine, Activity-based photosensitizers
  • İstanbul Teknik Üniversitesi Adresli: Hayır

Özet

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.