Prescription optimization and evaluation of in vitro targeting effects of liver cancer stem cell niche responsive multistep targeting liposomes
WANG Yuanyuan
JIANG Lingling
LI Shutong
KONG Liang
YAN Jie
LIU Zhen
XU Baoli
Abstract：Objective To prepare liver cancer stem cell niche responsive multistep targeting liposome loaded with doxorubicin(DOX)and XAV-939(CAP@CD133-D/X-Lip),and to evaluate its targeting effect in vitro.Methods Thin film dispersion-ammonium sulfate gradient method was used to prepare CAP@CD133-D/X-Lip.The optimal prescription and preparation process were optimized by Box-Behnken response surface method.The sensitivity of amphipathic peptides(CAP)in CAP@CD133-D/X-Lip was evaluated by determining the particle size changes of liposomes through adding fi-broblast activation protein(FAP-α).The in vitro targeting ability of different formulations to liver cancer stem cells(LCSCs)was investigated by cell uptake assay.Results The optimal formulation process was EPC 44 mg,Chol 2 mg,XAV-939 0.156 mg,DOX 1.16 mg,DSPE-PEG2000 2 mg,DSPE-PEG2000-MAL 2 mg,DSPE-PEG2000-CAP-PEG2000-UA-MC1110 2 mg,ultrasound power was 500 W,total prescription volume was 5 mL,and the average encapsulation efficiency of the two drugs was 79.79％±0.89％.The average particle size of CAP@CD133-D/X-Lip reduced to(95.56±2.32)nm after the addition of recombinant FAP-α protein,indicating that CAP@CD133-D/X-Lip had an excellent microenvironment re-sponse.The cell uptake experiment showed that CAP@CD133-D/X-Lip+FAP-α had a stronger uptake ability than CAP@CD133-D/X-Lip,indicating that its ability to target LCSCs was significantly enhanced.Conclusion CAP-responsive mul-tistep targeting liposomes to LCSCs are successfully prepared,and they have good microenvironment response and in vitro targeting ability.
Keywords：LiposomesDoxorubicinResponse surface methodLiver cancer stem cells
Publication Date：2024-10-28
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：7( 937-942,947 )