Novel Surfactant-like Hypocrellin Derivatives to Achieve Simultaneous Drug Delivery in Blood Plasma and Cell Uptake

Authors

  • Yang Zhang,

    1. Beijing National Laboratory for Molecular Sciences (BNLMS), Key Laboratory of Photochemistry, Institute of Chemistry, Chinese Academy of Sciences, Beijing, China
    Search for more papers by this author
  • Liming Song,

    1. Beijing National Laboratory for Molecular Sciences (BNLMS), Key Laboratory of Photochemistry, Institute of Chemistry, Chinese Academy of Sciences, Beijing, China
    Search for more papers by this author
  • Jie Xie,

    1. Beijing National Laboratory for Molecular Sciences (BNLMS), Key Laboratory of Photochemistry, Institute of Chemistry, Chinese Academy of Sciences, Beijing, China
    Search for more papers by this author
  • Haixia Qiu,

    1. Department of Laser Medicine, Chinese PLA General Hospital, Beijing, China
    Search for more papers by this author
  • Ying Gu,

    1. Department of Laser Medicine, Chinese PLA General Hospital, Beijing, China
    Search for more papers by this author
  • Jingquan Zhao

    Corresponding author
    1. Beijing National Laboratory for Molecular Sciences (BNLMS), Key Laboratory of Photochemistry, Institute of Chemistry, Chinese Academy of Sciences, Beijing, China
    Search for more papers by this author

Corresponding author email: zhaojq@iccas.ac.cn (Jingquan Zhao)

Abstract

Water-soluble derivatives of hypocrellins can be safely delivered in blood plasma but lose their photodynamic activity in vivo due to poor cell uptake, while hydrophobic derivatives retaining their activity may aggregate in the blood plasma and block vascular networks. Considering both drug delivery and biological activity, surfactant-like hypocrellin B (HB) derivatives, sodium 12-2-HB-aminododecanoate (SAHB) and sodium 11,11′-5,8-HB-dimercaptoundecanoate (DMHB), were first designed and then synthesized in the current work. Both SAHB and DMHB were photoactive, generating free radicals and reactive oxygen species, as confirmed by EPR and chemical measurements. Most importantly, DMHB was not only readily soluble, allowing preparation of an intravenous injection solution at a clinically acceptable concentration, but it was also more photodynamic therapy (PDT) active to human breast carcinoma MCF-7 cells than its parent HB under irradiation. The photodynamic activity was exactly identical to the 1O2 quantum yield and was not reduced by the improved water solubility, suggesting an independent hydrophilicity or lipophilicity. To our knowledge, this is a new strategy that possesses general significance for converting hydrophobic photosensitizers into clinically usable PDT drugs.

Ancillary