Wrapping Polyplex with a Monolayer of Rationally Designed Block Copolymer for Inter- and Intra-cellular Delivery of siRNA

We functionalized siRNA-loading polyplex by wrapping the particle with a rationally designed triblock copolymer membrane to prolong in vivo circulation, to prevent pre-mature disassembly and siRNA leaking, and to immobilize cell-targeting agent on the particle in optimized surface population. This triblock copolymer (named as ABCOO-) consists a steric stabilization block (polyethylene glycol, PEG) at outer surface, a hydrophobic block (polycaprolactone, PCL), to isolate the siRNA core, and a surface guiding block (surge conjugated multiple carboxylic groups) to lead the surface assembly. Selected cell-targeting agent may be conjugated to the distal end of the PEG block and immobilized on polyplex surface in an optimized population by mixing with non-conjugated ABCOO- in refined fractions prior to surface assembly. Noncovalent surface assembly of a functional polymer membrane may offer a promising method for prevention of siRNA leaking, flexibility in selecting cell targeting moieties, and convenience in optimizing surface population of the targeting agents.