Anti-gallbladder carcinoma activity of a novel nano-drug delivery system based on 3D cell culture model 

Objective To establish a three- dimensional ( 3D) cell culture model for gallbladder carcinoma ( GC) cells and to investigate the killing effect of a novel nano- drug delivery system on GC cells and its action mechanism. Methods Two- dimensional ( 2D) and 3D cell culture models for GC GBC- SD cells were established, and the normal cell toxicity of nano- drug delivery system ( CP24, folate receptor- mediated targeting poly ( epsilon- caprolactone) ) and the inhabitation rate of GC cells exposed to 5- fluorouracil ( 5- FU) carried by CP24 were determined by MTT assay, HE staining, flow cytometry ( FCM) , and Hoechst / PI staining. Results CP24 showed no significant cytotoxicity in liver and kidney cells, according to the result of HE staining. CP24 showed no significant killing effect on GC cells, according to the result of FCM. Given a 5- FU concentration of 100 μg / ml, the killing and inhibitory effects of both 5- FU- CP24 and 5- FU on GBC- SD cells were lower when using the 3D cell culture model than when using the 2D cell culture model; whether using a 2D or 3D cell culture model, 5- FU- CP24 had a significantly stronger killing effect on GBC- SD cells than 5- FU ( P < 0. 05) . 5- FU- CP24 mainly led to apoptosis in GBC- SD cells, while 5- FU mainly led to necrosis, as shown by Hoechst / PI staining. Conclusion 3D cell culture can reflect the intracellular microenvironment in vivo more accurately. Intercellular matrix may affect the cellular sensitivity to drugs. 5- FU can kill more GC cells when carried by a nano- drug delivery system. This degradable nano- drug delivery system has good drug delivery performance, sustained drug release, and high biosafety and holds promise for application in chemotherapy for GC.