Generation effect of Newkome dendrimers on cellular uptake

- Four generations of dendrimer peptide conjugates were synthesized.
- Each peptidodendrimer is able to enter HeLa cells via a combination of active and passive pathways.
- The second generation (G2) peptidodendrimer is the optimal generation for intracellular delivery.

Poly(amide)-based dendrimers can be used as delivery scaffolds in conjunction with the cell-penetrating peptide gH625 derived from the glycoprotein of the Herpes Simplex virus type 1. In this contribution, we aim to isolate the optimal dendrimer generation for cellular uptake for Newkome type dendrimers conjugated with gH625. For this study, we synthesized generations zero to three of the Newkome dendrimer-gH625 bioconjugate. Fluorescent microscopy experiments showed that the second and third generations are the most efficient for cellular uptake with the second generation having the synthetic advantage. The optimal second generation can be used as an improved material for a dendrimer based delivery scaffold for peptide therapeutics.

157