Cationic
polymers are used as non-viral vectors for
nucleic acid delivery. In this study, two biodegradable cationic
polymers were evaluated for the purpose of
siRNA delivery:
pHPMA-MPPM (poly((2-hydroxypropyl) methacrylamide 1-methyl-2-piperidine methanol)) and TMC (O-methyl-free N,N,N-trimethylated
chitosan). The silencing activity and the cellular cytotoxicity of polyplexes based on these biodegradable
polymers were compared with those based on non-biodegradable
pDMAEMA (poly(2-dimethylamino)ethyl methacrylate) and PEI (
polyethylenimine) and with the regularly used lipidic transfection agent
Lipofectamine. To promote endosomal escape, either the endosomolytic
peptide diINF-7 was added to the formulations or photochemical internalization (PCI) was applied. Incubation of H1299 human
lung cancer cells expressing
firefly luciferase with polyplexes based on
pHPMA-MPPM and TMC showed 30-40% silencing efficiency. This silencing activity was equal to or better than that obtained with the standard transfectants. Under all experimental conditions tested, the cytotoxicity of the biodegradable
polymers was low. The application of PCI, as well as the addition of the diINF-7
peptide to the formulations increased their silencing activity up to 70-80%. This demonstrates that
pHPMA-MPPM- and TMC-based polyplexes benefit substantially from endosomal escape enhancement. Importantly, the polyplexes retained their silencing activity in the presence of serum, and they showed low cytotoxicity. These biodegradable vectors are therefore attractive systems for further in vivo evaluations.