抄録
Methoxy-PEG-b-siRNAs possessing 27 base pairs siRNA (27 bp-siRNA) and 21 base pairs siRNA (21 bp-siRNA) were successfully synthesized via the Michael addition reaction of 5'-thiol modified siRNA and poly(ethylene glycol) (PEG) bearing an acrylate group at omega-end. PEGylated polyplexes were prepared through the self-assembly of poly(N-3,6-diazahexyl aspartic acid amide) (P[Asp(DET)]) and each of PEG-siRNA conjugates bearing an endosomal pH-responsive linkage between PEG chain and siRNA. The stability of the PEGylated polyplexes containing 27 bp-siRNA segment with various ratios of the number of protonated amino group units per nucleotide (N+/P ratios) was compared with that of the PEGylated polyplexes containing 21 bp-siRNA segment by means of polyacrylamide gel electrophoresis. Worth noticing that complete retardation of the conjugate was observed at an N+/P ratio 3 for PEGylated polyplex composed of PEG-27 bp-siRNA conjugate, whereas the PEGylated polyplex composed ofPEG-21 bp-siRNA showed the complete retardation of the conjugate at N+/P ratio 5. This result indicate that longer siRNA segment in conjugate contributes to the improvement of the stability of PEGylated polyplexes due to the increase in the electrostatic interactions.
