New, Hydrophilic, HPMA-Based Polymers for Bioresponsive Shielding of Gene-Delivery Vectors

New, hydrophilic polymers and copolymers based on HPMA, carrying reactive thiazolidine-2-thione groups either situated at the polymer chain end or randomly distributed along the chains bound to the polymer backbone via spacers containing reductively degradable disulfide linkages, have been developed for an efficient and intracellularly removable coating of gene-delivery vectors. Amino-group-bearing PS-latex nanoparticles and self-assembled poly(L-lysine)/DNA complexes were used as models for gene-delivery viral and nonviral vectors to study the coating reaction with reactive HPMA-based (co)polymers. It is shown that modification of the particles was effective, resulting in an increase in the (M) over bar (w) and R-h of the particles, which depend on the polymer length and its detailed structure. Incubation of the coated particles in buffers modeling the intracellular environment induced unshielding of the vectors and release of the polymer layer from their surface.