Singlet oxygen-activatable Paclitaxel prodrugs via intermolecular activation for combined PDT and chemotherapy

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:29

Article

Bio, Moses¹  Mahabubur, Kazi Md¹  Lim, Irene¹  Rajaputra, Pallavi¹  Hurst, Robert E.²  You, Youngjae^1,3 

[1] Univ Oklahoma, Coll Pharm, Dept Pharmaceut Sci, Oklahoma City, OK 73117 USA

[2] Univ Oklahoma, Hlth Sci Ctr, Dept Urol, Oklahoma City, OK 73117 USA

[3] Univ Oklahoma, Dept Chem & Biochem, Norman, OK 73019 USA

关键词: Photo-unclick;    Paclitaxel;    Photodynamic therapy;    Singlet oxygen;   

DOI  :  10.1016/j.bmcl.2019.03.053

来源: Elsevier

【 摘 要 】

Systemic side effects and high hydrophobicity are major disadvantages of paclitaxel (PTX), one of the most popular anticancer drugs. Here, we present singlet oxygen (50)-activatable and mitochondria-targeted PTX prodrugs to overcome these problems and boost the cytotoxic effect of photodynamic therapy (PDT). Three PTX prodrugs were prepared by conjugating PTX with various cationic groups. Hydrophobicity was determined in LogD(7,4) value. Mitochondrial localization was confirmed by fluorescence confocal microscopy and uptake of mitochondria-specific fluorescence probe. Dark- and photo-toxicity were measured in AY-27 cells with MTT assay. All three prodrugs showed better hydrophilicity than PTX and improved phototoxicity when combined with protoporphyrin IX (PpIX) PDT. In conclusion, SO-activatable and higher hydrophilic PTX prodrugs were successfully prepared. This approach could be used to improve the antitumor efficacy of PDT without the systemic side effects of PTX.

【 授权许可】

Free