The
decoration of polyamidoamine (PAMAM) dendrimers with some functional
moieties holds promises for improving the gene-delivery behavior of
the resulting polyplexes. Herein, we reported the synthesis and the
development of non-viral gene vectors built on an array of PAMAMs,
spanning generation 2 (G2), G4, and G7, specifically tethered with
multivalent neomycin (Neo) or guanidinoneomycin (GNeo). Following
a thorough chemical characterization by means of NMR and MALDI analyses,
the ability of PAMAM–(G)Neo conjugates to serve as transfectants
was investigated. First, we demonstrated that every PAMAM, whether
or not tethered with Neo (or GNeo), exhibited greater DNA packing
ability than the gold standard transfectant 25 kDa bPEI. Measurements of the colloidal properties showed that PAMAMs,
when mixed with plasmid DNA (pDNA) as a function of the nitrogen-to-phosphate
ratio (N/P), allowed preparing complexes of ≈150–300
nm in diameter with a positive surface charge of ≈+20–35
mV, strictly dependent on the PAMAM generation. The conjugation with
Neo affected the DNA release behavior from PAMAM-based polyplexes
and their ultimate transfection efficiency. When low generation PAMAM
G2 was tethered with Neo, we obtained the most efficient transfectants,
with remarkable antibacterial activity against Gram negative bacteria.
It is worth noting that pDNA/PAMAM–(G)Neo nanoassemblies, which
were tested at the optimal N/P, invariably showed better transfection
efficiency than 25 kDa bPEI, along with low cytotoxicity
in both HeLa and COS-7 cells. Altogether, these results underline
the potential of such PAMAM–(G)Neo dendrimers as promising
vehicles for efficient gene delivery into cells.