Using folic acid-modified polyethylenimine-SPIO nanoparticles for PD-L1 siRNA delivery to target gastric cancer / 中国病理生理杂志

ABSTRACT

AIM: To synthesis and characterize a multi-functional siRNA delivery agent with effective thera-peutic effects and MR-tracing ability for programmed death ligand-1 ( PD-L1 ) positive gastric cancer SGC-7901 cell line . METHODS:The characterization , binding ability , cytotoxicity , transfection efficiency and cellular internalization of the polyplex were determined .The PD-L1 knockdown effect was analyzed , and cytokines secreted by cocultured T cells were measured.RESULTS:We developed folic acid (FA)-PEG-SS-PEI-SPION as siRNA delivery agent for PD-L1 knockdown. At N/P ratio of 10, the FA-PEG-SS-PEI-SPION bound PD-L1 siRNA to form polyplex in a diameter of (116.7 ±2.5) nm with zeta potential of (9.14 ±0.80) mV.Transfection efficiency of the targeted polyplex was (95.06 ±0.44)%, com-pared with ( 93.87 ±1.05 )% of the untargeted polyplex .Mean fluorescence intensity of the targeted polyplex was 1892.67 ±81.51, significantly higher than 1324.33 ±186.58 of the untargeted.The cellular magnetic resonance (MR) imaging showed the polyplex also acted as T 2 weighted contrast agent for cancer MR imaging .The relative mRNA level of PD-L1 in polymer/siRNA-2 treatment group was (9.07 ±0.79)%.Decreased protein expression of PD-L1 was showed by Western blot .The secretion levels of IFN-γand TNF-αin cocultured T cells increased , while that of IL-10 decreased . CONCLUSION:Our findings highlighted the potential of the multifunctional theranostic nanoparticles for effective targe -ting PD-L1 knockdown therapy and MR imaging diagnosis in gastric cancers .