In this study, shell crosslinked knedel-like (SCK) nanoparticles composed of biodegradable poly(lactic acid) (PLA) core were prepared by the supramolecular self-assembly of an amphiphilic diblock copolymer synthesized by a combination of ring opening polymerization (ROP) and reversible addition-fragmentation chain transfer (RAFT) polymerization.  Enzymatic degradation of the PLA cores of the nanoparticles was achieved upon the addition of an ester- and amide-degrading enzyme.  As cationic nanoparticles are a promising class of transfection agents for oligonucleotide and gene delivery, synthetic methodologies were developed for the conversion of the negatively-charged shell of the enzymatically-degradable SCKs to positively-charged cationic SCK (cSCK) nanoparticles for the complexation of nucleic acids.  In addition to the exciting possibility of these degradable cSCK nanoparticles serving as vessels for efficient intracellular delivery of nucleic acids, the hydrolysis of the PLA core and crosslinkers may provide a mechanism for programmed disassembly of the cSCK nanoparticles within endosomes, and release of therapeutics from the nanoparticles.

Development of degradable cationic shell crosslinked nanoparticles toward efficient transfection of nucleic acids

244th National Meeting (2012)

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