Fluorescent Polyamines for Efficient DNA Condensation and Cellular Uptake

Polyamine-based carriers, including spermine and spermidine, offer significant potential due to their ability to bind DNA and facilitate cellular uptake. In this study, four fluorophore-tagged spermidine and spermine derivatives (S1C, S2C, S1D, S2D) linked by a non-cleavable linker are synthesized and evaluated for their ability to condense DNA and mediate gene delivery. Spectroscopic and bio-AFM studies confirm the DNA condensation, with S2C exhibiting selective lysosomal targeting and photostability for up to 2 h. Further validation using an RFP-tagged plasmid confirms S2C’s effective DNA internalization. This approach offers a promising, straightforward alternative for gene delivery, addressing key limitations of conventional methods. However, further optimization is needed to improve gene release and enhance the therapeutic efficacy.