The effect of Amine modification on siRNA delivery of redox-responsive PEGylated amphiphilic micellar nanoparticles for triple negative breast cancer therapy

Abstract

We developed a set of methoxypoly(ethyleneglycol)-co-poly(N3-ε-caprolactone) (mPEG-N3PCL)copolymers with different types of amine linkers and investigated thecontribution of the introduced amino linker to the gene delivery efficiency ofnanoparticles. The nanoparticles were crosslinked from the caprolactone regionswith a redox-responsive linker. Formulation variables including Redox-crosslinkingand N:P ratio were examined to obtain nanoparticles with optimal size andhighest siRNA entrapment efficacy (EE). The nanoparticles were characterized byDLS, and nanodrop UV-vis spectroscopy. Nanoparticle size, polydispersity index and siRNAentrapment efficacy were found to depend on the all the examined formulationvariables specially the N:P ratio. The formulation with N:P ratio of 5 with56.13 nm in size and 92.24% EE was chosen as the optimal formulation.Controllable size, loading efficiency and releasepattern by redox-responsivity make this class of novel carriers a promisingcandidate for tumour targeted gene delivery applications.