Related Experiment Video
Updated: May 17, 2026
Predicting Gene Silencing Through the Spatiotemporal Control of siRNA Release from Photo-responsive Polymeric Nanocarriers
Published on: July 21, 2017
A combinatorial library of bi-functional polymeric vectors for siRNA delivery in vitro
1School of Chemical and Biomolecular Engineering, Cornell University, Ithaca, New York 14853, USA.
Purpose:
To apply a combinatorial chemistry approach toward the design of polymeric vectors, and to evaluate their effectiveness as siRNA delivery systems in vitro.
Methods:
Poly(acrylic acid) (pAA) was synthesized via RAFT polymerization with well-controlled molecular weights (M (n): 3 kDa, 5 kDa, 10 kDa and 21 kDa). A polymer library was generated from the pAA precursors by conjugating two distinct moieties, agmatine (Agm) and D-(+)-galactosamine (Gal), at various ratios. Biophysical and cellular characterization was evaluated in vitro for these polymeric vectors using MDA-MB-231-luc+ cells.
Results:
A critical balance between Agm/Gal content and polymer molecular weight must be attained to achieve favorable transfection efficacies. From the library of 22 polymers, only a few had knockdown efficiencies commensurate with effective siRNA delivery, particularly those with polymer precursor M (n) of 5 kDa and 10 kDa. Highest protein knockdown of 84% was achieved by a polymer conjugate with a 5 kDa pAA backbone with a side chain composition of 55% Agm and 17% Gal.
Conclusions:
Effective delivery of siRNA was found to be highly dependent on the molecular structure of the polymeric vector. The combinatorial approach employed provided the tools to identify optimal structural properties leading to efficient siRNA delivery for this class of vector.
