Abstract
Traditional nanosized drug delivery systems have the disadvantages of low drug loading and poor targeting. Rhein, one of the active free anthraquinones extracted from rhubarb, has been reported to show anti-cancer activity. In this study, folic acid-polyethylene glycol2000-rhein (FA-PEG-RH) conjugate nanomicelles were designed and prepared to increase the drug loading capacity and enhance the nanomicelle targeting ability. The drug loading and encapsulation efficiency of the rhein-loaded FA-PEG-RH nanomicelles were 8.13% ± 0.92% and 82.03% ± 9.1%, respectively. In vitro fluorescence imaging showed FA-PEG-RH nanomicelles can penetrate HepG2 cell membranes in 4 h. The MTT test of HeLa cells showed the unloaded FA-PEG-RH micellar carrier itself showed anti-tumor activity. The RH -loaded FA-PEG-RH nanomicelles can improve the stability of rhein in rat plasma. The cytotoxicity of M109 cells in vitro and the anti-tumor test of HeLa cells tumor-bearing nude mice in vivo demonstrated that RH or zinc phthalocyanine (ZnPc)-loaded FA-PEG-RH nanomicelles can exert the synergistic anti-tumor effect owing to the conjugate's cell proliferation inhibition and ZnPc's photosensitive property. The FA-PEG-RH nanomicelles are expected to be used for the carrier of various water-insoluble anti-tumor drugs in the pharmaceutical industry.
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