Highly branched poly(β-amino ester)s with thiolated branching units for gene delivery

Highly branched poly(β-amino ester)s (HPAEs) are among the most promising candidates for gene delivery. However, so far, all HPAEs have been synthesized primarily via Michael addition with triacrylates, tetraacrylates or diamines as branching monomers. Here we report the development of HPAEs with thiolated branching units. By using pentaerythritol tetrakis(3-mercaptopropionate) (PTMP) as the branching monomer, two HPAEs with similar molecular weights but different branching degrees were synthesized. The results show that both HPAEs effectively condense DNA into nanosized polyplexes with positive zeta potentials. HPAE-1/DNA polyplexes were capable of transfecting both the human cervical cancer cell line (HeLa) and the difficult-to-transfect human bladder transitional cell carcinoma (UM-UC-3). The maximum transfection efficiency of HPAE-1 was lower than that of linear poly(β-amino ester) (L-C32) and HPAE containing tetraacrylate branching units (ER-HPAE-1), but comparable to that of star-shaped PAE with a diamine core (SPAE-1-5 h) and branched PEI 25k, with high cell viability. This study develops a new class of HPAEs with thiolated branching units, expanding the chemical diversity of the HPAE family.