Here, we present a modular synthesis as well as physicochemical and biological evaluation of a new series of amphiphilic dendrons carrying triphenylphosphonium groups at their periphery. Within the series, the size and mutual balance of lipophilic and hydrophilic domains are systematically varied, changing the dendron shape from cylindrical to conical. In physiological solution, the dendrons exhibit very low critical micelle concentrations (2.6-4.9 μM) and form stable and uniform micelles 6-12 nm in diameter, depending on dendron shape; the results correlate well with molecular dynamics simulations. The compounds show relatively high cytotoxicity (IC50 1.2-21.0 μM) associated with micelle formation and inversely related to the size of assembled particles. Depending on their shape, the dendrons show promising results in terms of dendriplex formation and antibacterial activity. In addition to simple amphiphilic dendrons, a fluorescently labeled analogue was also prepared and utilized as an additive visualizing the dendron's cellular uptake.

Biomedical Research Centre University Hospital Hradec Králové Sokolská 581 500 05 Hradec Králové Czech Republic

Centre for Nanomaterials and Biotechnology Faculty of Science Jan Evangelista Purkyně University in Ústí nad Labem Pasteurova 3632 15 400 96 Ústí nad Labem Czech Republic

Department of Epidemiology Military Faculty of Medicine University of Defence Třebešská 1575 500 05 Hradec Králové Czech Republic

Department of Physics University of Jan Evangelista Purkyně in Ústí nad Labem 400 96 Ústí nad Labem Czech Republic

The Czech Academy of Sciences Institute of Chemical Process Fundamentals 165 02 Prague Czech Republic

Université Bordeaux CNRS Bordeaux INP CBMN UMR 5248 F 33600 Pessac France

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