pH-responsive
dual-loaded nanoplatforms based on polyamidoamine
dendrimer with a hydroxyl-terminated surface (PAMAM–OH), generations
3, 4, and 5 (G3, G4, and G5, respectively), were loaded with Peganum harmala alkaloid extracts (H) and tannic acid (TA)
and tested against breast cancer cells. G3 dendrimers encapsulating
the drugs showed the smallest sizes, PDI, and highest ζ-potential
and entrapment efficiencies compared to those of G4 and G5. G3 dendrimers
loaded with either doxorubicin (DOX), H, or TA or dual-loaded with
H+TA were prepared. The average diameters of the designed DOX@G3,
H@G3, TA@G3, and H+TA@G3 NPs were 78 ± 5.1, 122 ± 3.7, 141
± 2.8, and 192 ± 1.9 nm, respectively. All of the prepared
NPs exhibited high positive surface charges and high entrapment efficiencies.
Release studies showed the ability of the dendrimers to release their
cargo selectively in the cancerous cells’ extracellular pH
(pH 5.5) via a pH-triggered mechanism while maintaining an outstanding
stability at physiological conditions (pH 7.4). Furthermore, H@G3,
TA@G3, and H+TA@G3 NPs exhibited remarkable cytotoxic activities against
breast adenocarcinoma (MCF-7) cells with IC50 values of
2.6 ± 0.08, 4.5 ± 0.9, and 1.7 ± 0.6 μg/mL, respectively,
as compared to free H, free TA, free DOX, and DOX@G3 (IC50 values of 5.8 ± 0.8, 7.2 ± 1, 6.75 ± 0.7, and 4.7
± 0.8 μg/mL). The formulated H@G3, TA@G3, and DOX@G3 exhibited
11.8, 9.3, and 5.3% increases in late apoptosis in MCF-7 cells relative
to their respective free forms, while H+TA@G3 exhibited the highest
percentage of late apoptosis in MCF-7 cells. In conclusion, G3 PAMAM–OH
dendrimers dually loaded with Peganum harmala alkaloids
and tannic acid hold the potential for effective treatment of breast
cancer.