Atomic force microscopic analysis of the influence of the molecular weight of poly(L)lysine on the size of polyelectrolyte complexes formed with DNA.

We are developing self-assembling micellar vehicles based on multifunctional block copolymers as well-defined synthetic vehicles suitable for safe in vivo delivery of DNA. As a first stage, DNA expression vectors (6 kb) were condensed with poly(L)lysine of different molecular weights (3970-224 500) to form polyelectrolyte complexes and analysed by atomic force microscopy (AFM). Discrete complexes were formed in every case, although the highest molecular weight poly(L)lysine preparation (224 500) produced large complexes with significant polydispersity (diameters ranging from 120-300 nm), while the smallest poly(L)lysine (3970) produced more homogeneous complexes with diameters ranging from 20-30 nm. Poly (L)lysine preparations of molecular weight 53 700 and 23 800 produced complexes of intermediate size and poly-dispersity. The mean volumes of the complexes formed using poly(L)lysine 224 500 and 3970 were 606 000 nm3 and 3700 nm3, respectively. Polyelectrolyte complexes formed using low molecular weight poly(L)lysine also showed significantly decreased cytotoxicity. Given restrictions of access to many cellular targets and the need for good biocompatibility, synthetic vectors based on DNA condensed with low molecular weight polycations may be more appropriately developed for general use.