Enhanced Bioactivity of Internally Functionalized Cationic Dendrimers with PEG Cores
Abstract
Hybrid dendritic-linear block copolymers based on a 4-arm poly(ethylene glycol) (PEG) core were synthesized using an accelerated AB2/CD2 dendritic growth approach through orthogonal amine/epoxy and thiol-yne chemistries. The biological activity of these 4-arm and the corresponding 2- arm hybrid dendrimers revealed an enhanced, dendritic effect with an exponential increase in cell internalization concomitant with increasing amine end groups and low cytotoxicity. Furthermore, the ability of these hybrid dendrimers to induce endosomal escape combined with their facile and efficient synthesis makes them attractive platforms for gene transfection. The 4-arm-based dendrimer showed significantly improved DNA binding and gene transfection capabilities in comparison with the 2-arm derivative. These results combined with the MD simulation indicate a significant effect of both the topology of the PEG core and the multivalency of these hybrid macromolecules on their DNA binding and delivery capabilities.
Document Details
- Document Type
- Technical Report
- Publication Date
- Nov 09, 2012
- Accession Number
- ADA609412
Entities
People
- Christoph Brauchle
- Craig Hawker
- Elizabeth Amir
- Fabrizio Salomone
- Frauke M. Mickler
- Giovanni M. Pavan
- Giuseppe Bardi
- Kato L. Killops
- Lorenzo Albertazzi
- Mariangela Panniello
- Roey J. Amir
- Taegon Kang
Organizations
- University of California, Santa Barbara