Abstract: Objective We aim to construct lipid nanoparticles loaded with siRNA targeting IKKβ and explore their ability to inhibit choroidal neovascularization(CNV)by repolarizing the macrophage phenotype. Methods Cationic lipid nanoparticles were prepared by thin film dispersion, and the optimal gene nanoparticle loading ratio was screened for by agarose gel electrophoresis. Particles were characterized using transmission electron microscopy and a Malvern particle sizer; Expression of IKKβmRNA and mRNAs encoding molecules associated with macrophage polarization phenotype in M2 cells was detected via qRT-PCR; Expression of IKKβprotein in M2 cells was detected by Western blotting. A laser-induced CNV model was established in mice and used to investigate treatment. Macrophage phenotypic molecular protein expression in CNV lesions after drug administration was detected by Western blotting. The therapeutic effect of gene loaded nanoparticles on CNV was detected by OCTA. Results LNs-siIKKβ were successfully prepared. Particle size was(133.3±0.62)nm, and zeta potential was(6.72±0.17)mV at the optimal loading ratio. In vitro, macrophages can be repolarized from M2 to M1 phenotype by suppressing IKKβ expression in M2-type macrophages using LNs-siIKKb. In vivo, after treatment, macrophages in CNV lesions tended to repolarize from M2 to M1 phenotype and CNV production was suppressed. Conclusion The constructed siIKKβ-loaded cationic lipid nanoparticles were able to repolarize macrophages from M2 to M1 in vitro and in CNV lesions in vivo, and inhibited the generation of CNV.

Key words: Cationic lipid nanoparticles, IKKβ, Macrophage polarization, Choroidal neovascularization