The
development of nonviral dendritic polymers with a simple molecular
backbone and great gene delivery efficiency to effectively tackle
cancer remains a great challenge. Phosphorus dendrimers or dendrons
are promising vectors due to their structural uniformity, rigid molecular
backbones, and tunable surface functionalities. Here, we report the
development of a new low-generation unsymmetrical cationic phosphorus
dendrimer bearing 5 pyrrolidinium groups and one amino group as a
nonviral gene delivery vector. The created AB5-type dendrimers with simple molecular backbone can compress microRNA-30d
(miR-30d) to form polyplexes with desired hydrodynamic sizes and surface
potentials and can effectively transfect miR-30d to cancer cells to
suppress the glycolysis-associated SLC2A1 and HK1 expression, thus
significantly inhibiting the migration and invasion of a murine breast
cancer cell line in vitro and the corresponding subcutaneous
tumor mouse model in vivo. Such unsymmetrical low-generation
phosphorus dendrimers may be extended to deliver other genetic materials
to tackle other diseases.