The Effect and Role of Carbon Atoms in Poly(β-amino
ester)s for DNA Binding and Gene Delivery
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Abstract
Polymeric vectors for gene delivery
are a promising alternative
for clinical applications, as they are generally safer than viral
counterparts. Our objective was to further our mechanistic understanding
of polymer structure–function relationships to allow the rational
design of new biomaterials. Utilizing poly(β-amino ester)s (PBAEs),
we investigated polymer–DNA binding by systematically varying
the polymer molecular weight, adding single carbons to the backbone
and side chain of the monomers that constitute the polymers, and varying
the type of polymer end group. We then sought to correlate how PBAE
binding affects the polyplex diameter and ζ potential, the transfection
efficacy, and its associated cytotoxicity in human breast and brain
cancer cells in vitro. Among other trends, we observed in both cell
lines that the PBAE–DNA binding constant is biphasic with the
transfection efficacy and that the optimal values of the binding constant
with respect to the transfection efficacy are in the range (1–6)
× 10<sup>4</sup> M<sup>–1</sup>. A binding constant in
this range is necessary but not sufficient for effective transfection