文獻名： Cytosolic Delivery of Doxorubicin from Liposomes to Multidrug-Resistant Cancer Cells via Vaporization of Perfluorocarbon Droplets

 

作者： Jacob B Williams¹, Clara M Buchanan¹, Ghaleb Husseini² and William G Pitt¹

1 Department of Chemical Engineering, Brigham Young University, USA

2 Department of Chemical Engineering, American University of Sharjah, UAE

 

摘要：A  common  mechanism  of  multidrug  resistance  is  the  upregulation  of  efflux  pumps in the cancer cells that can more rapidly export unwanted materials (e.g. cancer  drugs)  out  of  the  cell,  compared  to  sensitive  cancer  cells.  This  research  seeks  to  overcome  this  mechanism  by  vaporizing  a  perfluoropentane  emulsion  droplet inside of a drug-containing liposome (eLiposome) that was endocytosed into  a  cancer  cell.  Folate  attached  to  the  eLiposome  facilitates  uptake  into  the  cell as observed by confocal microscopy. Ultrasound was examined as a trigger to initiate the vaporization of the perfluoropentane droplet and release doxorubicin from  folated  eLiposomes  (feLD).  Two  seconds  of  ultrasound  released  78%  of  encapsulated  doxorubicin  from  feLD.  Doxorubicin-sensitive  KB-3-1  cells  and  doxorubicin-resistant  KB-V1  cells  treated  with  feLD  (without  ultrasound)  had  cell viabilities of 33% and 60%, respectively. Ultrasound had negligible additional effect on the cell viability of KB-3-1 and KB-V1 cells treated with feLD (33% and 53%, respectively). We hypothesized that the doxorubicin sulfate fibers that were formed  during  the  loading  of  doxorubicin  into  the  eLiposome  present  a  site  for  heterogeneous  nucleation  once  the  feLD  is  endocytosed  by  the  cell,  and  thus  droplet vaporization occurs with or without ultrasound.