Preparation and in vitro evaluation of reduction-sensitive prodrug nanoparticles for coloaded DOX and siRNA
OBJECTIVE To construct a kind of reduction-sensitive prodrug nanoparticles(PSCSD NPs)for coloaded doxo-rubicin(DOX)and siRNA,and to evaluate its physicochemical properties,cellular uptake and in vitro cytotoxicity.METHODS Carboxymethyl chitosan-disulfide bond-DOX(CMC-SS-DOX)was characterized by 1H nuclear magnetic resonance spectroscopy(1H NMR)and Fourier transform infrared spectroscopy(FT-IR).PSCSD NPs were prepared by ultrasonic method,and the properties,such as particle size,drug loading,encapsulation efficiency,serum stability,hemolysis rate and in vitro release behav-ior,were investigated.Both fluorescence microscopy and flow cytometry were used to determine the uptake of PSCSD NPs by 4T1 cells.MTT assay was used to determine the cytotoxicity of PSCSD NPs in vitro.RESULTS CMC-SS-DOX was success-fully synthesized.The particle size of PSCSD NPs was(155.1±4.0)nm(PDI=0.144±0.028).The Zeta potential was(-29.9± 1.0)mV,the drug loading was(8.25±0.47)％,and the encapsulation efficiency was(78.41±4.52)％.The prepared PSCSD NPs were spherical with good blood compatibility and serum stability.PSCSD NPs had reductive response drug release properties and were expected to release drugs quickly at the tumor site.The results of cell uptake and MTT assay showed that PSCSD could efficiently co-delivery DOX and siRNA into tumor cells to exert anti-tumor effect.CONCLUSION The PSCSD NPs were suc-cessfully prepared and co-loaded with DOX and siRNA to achieve synergistic efficiency between chemotherapy and immunotherapy.
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