Functionalized linear poly(amidoamine)s are efficient vectors for intracellular protein delivery
Coue, G; Engbersen, JFJ
| HERO ID | 1461794 |
|---|---|
| In Press | No |
| Year | 2011 |
| Title | Functionalized linear poly(amidoamine)s are efficient vectors for intracellular protein delivery |
| Authors | Coue, G; Engbersen, JFJ |
| Journal | Journal of Controlled Release |
| Volume | 152 |
| Issue | 1 |
| Page Numbers | 90-98 |
| Abstract | An effective intracellular protein delivery system was developed based on functionalized linear poly(amidoamine)s (PAAs) that form self-assembled cationic nanocomplexes with oppositely charged proteins. Three differently functionalized PAAs were synthesized, two of these having repetitive disulfide bonds in the main chain, by Michael-type polyaddition of 4-amino-1-butanol (ABOL) to cystamine bisacrylamide (CBA), histamine (HIS) to CBA, and ABOL to bis(acryloyl)piperazine (BAP). These water-soluble PAAs efficiently condense β-galactosidase by self-assembly into nanoscaled and positively-charged complexes. Stable under neutral extracellular conditions, the disulfide-containing nanocomplexes rapidly destabilized in a reductive intracellular environment. Cell-internalization and cytotoxicity experiments showed that the PAA-based nanocomplexes were essentially non-toxic. β-Galactosidase was successfully internalized into cells, with up to 94% of the cells showing β-galactosidase activity, whereas the enzyme alone was not taken up by the cells. The results indicate that these poly(amidoamine)s have excellent properties as highly potent and non-toxic intracellular protein carriers, which should create opportunities for novel applications in protein delivery. |
| Doi | 10.1016/j.jconrel.2011.01.023 |
| Pmid | 21277918 |
| Wosid | WOS:000292718200012 |
| Is Certified Translation | No |
| Dupe Override | No |
| Comments | Source: Web of Science WOS:000292718200012 |
| Is Public | Yes |
| Language Text | English |
| Keyword | Bioreducible polymers; Disulfide reduction; Intracellular protein delivery; Poly(amidoamine); Polyelectrolyte complex |