A biophysical study on the mechanism of interactions of DOX or PTX with α-lactalbumin as a delivery carrier Academic Article uri icon

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abstract

  • Doxorubicin and paclitaxel, two hydrophobic chemotherapeutic agents, are used in cancer therapies. Presence of hydrophobic patches and a flexible fold could probably make α-Lactalbumin a suitable carrier for hydrophobic drugs. In the present study, a variety of thermodynamic, spectroscopic, computational, and cellular techniques were applied to assess α-lactalbumin potential as a carrier for doxorubicin and paclitaxel. According to isothermal titration calorimetry data, the interaction between α-lactalbumin and doxorubicin or paclitaxel is spontaneous and the K (M-1) value for the interaction of α-lactalbumin and paclitaxel is higher than that for doxorubicin. Differential scanning calorimetry and anisotropy results indicated formation of α-lactalbumin complexes with doxorubicin or paclitaxel. Furthermore, molecular docking and dynamic studies revealed that TRPs are not involved in α-Lac's interaction with Doxorubicin while TRP 60 interacts with paclitaxel. Based on Pace analysis to determine protein thermal stability, doxorubicin and paclitaxel induced higher and lower thermal stability in α-lactalbumin, respectively. Besides, fluorescence lifetime measurements reflected that the interaction between α-lactalbumin with doxorubicin or paclitaxel was of static nature. Therefore, the authors hypothesized that α-lactalbumin could serve as a carrier for doxorubicin and paclitaxel by reducing cytotoxicity and apoptosis which was demonstrated during our in vitro cell studies.

authors

  • Delavari, Behdad
  • Mamashli, Fatemeh
  • Bigdeli, Bahareh
  • Poursoleiman, Atefeh
  • Karami, Leila
  • Zolmajd-Haghighi, Zahra
  • Ghasemi, Atiyeh
  • Samaei-Daryan, Samaneh
  • Hosseini, Morteza
  • Haertlé, Thomas
  • Muronetz, Vladimir I
  • Halskau, Øyvind
  • Moosavi-Movahedi, Ali Akbar
  • Goliaei, Bahram
  • Rezayan, Ali Hossein
  • Saboury, Ali Akbar

publication date

  • December 2018

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