Intracellular delivery of DNA and enzyme in active form using degradable carbohydrate-based nanogels.Mol Pharm. 2012 Nov 05; 9(11):3160-70.MP
The facile encapsulation of biomolecules along with efficient formulation and storage makes nanogels ideal candidates for drug and gene delivery. So far, nanogels have not been used for the codelivery of plasmid DNA and proteins due to several limitations, including low encapsulation efficacy of biomolecule of similar charges and the size of cargo materials. In this study, temperature and pH sensitive carbohydrate-based nanogels are synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization technique and are studied in detail for their capacity to encapsulate and codeliver plasmid DNA and proteins. The temperature sensitive property of nanogels allows the facile encapsulation of biomaterials, while its acid-degradable profile allows the burst release of biomolecules in endosomes. Hence these materials are expected to serve as efficient vectors to deliver biomolecules of choice either alone or as codelivery system. The nanogels produced are relatively monodisperse and are around 30-40 nm in diameter at 37 °C. DNA condensation efficacy of the nanogels is dependent on the hydrophobic property of the core of the nanogels. The DNA-nanogel complexes are formed by the interaction of carbohydrate residues of nanogels with the DNA, and complexes are further stabilized with linear cationic glycopolymers. The DNA-nanogels complexes are also studied for their protein loading capacity. The degradation of the nanogels and the controlled release of DNA and proteins are then studied in vitro. Furthermore, the addition of a nontoxic, cationic glycopolymer to the nanogel-DNA complexes is found to improve the cellular uptake and hence to improve gene expression.