Abstract
For safe and effective delivery of nucleic acid, a series of tunable membrane-penetrating nanogels were developed, which were constructed from reversibly cross-linked guanidinylated poly(L-lysine) dendrimers with various guanidination degrees and cross-linking degrees. The designed nanogels electrostatically interacted with DNA, resulting in condensed nanogelplexes with size of about 100 nm and positive zeta potential of 35 mV. Increased DNA complexing ability of nanogels can be achieved via increasing the guanidination degree. The presence of reductive agents gave rise to cleavage of disulfide bonds in PK3G30D2, in accompany with the collapse and swelling of nanogelplexes. Compared with PEI and PK3D2 lacking of guanidine groups, PK3G30D2 bearing 30 guanidine groups exhibited the highest transfection performance with good biocompatibility in serum-containing medium. Meanwhile, guanidination in collaboration with reversible cross-linking also promoted cellular internalization, lysosomal escape and release of DNA from condensed nanogelplexes, resulting in substantially improved transfection synergistically. The enhanced transfection efficiency by the guanidine-rich PK3G30D2 was also achieved in tibialis anterior muscles and tumor xenografts in mice. These results reveal these bioreductive and guanidinylated nanogels with synergistic effects might hold great potential for developing gene delivery system.
Original language | English |
---|---|
Article number | 100646 |
Journal | Applied Materials Today |
Volume | 20 |
DOIs | |
State | Published - Sep 2020 |
Keywords
- Gene delivery
- Guanidine groups
- Nanogel
- Peptide dendrimer
- Reversible cross-linking