Abstract
Gold nanorods (GNRs) show promising biomedical therapeutic/imaging applications. This study investigated the effect of PEGylated-GNRs on the angiogenesis factors: vascular endothelial growth factor (VEGF) and platelet derived growth factor (PDGF) and their regulator (miR-29a-3p) under variable administration conditions-dosage, gender, routes of administration, and post-treatment intervals. In CD-1 mice of both genders, PEG-GNRs (94, 375, 750, and 1500 ng/kg body weight, similar to 40 nm, aspect ratio similar to 4.5) were injected via different routes: intravenous, subcutaneous, and intramuscular, and then VEGF and PDGF were estimated in sera by ELISA, after post-treatment intervals (1, 3, and 7 days). Low doses of PEG-GNRs (94 and 375 ng/kg body weight) resulted in anti-angiogenic effects, while the highest dose (1500 ng/kg body weight) provoked a pro-angiogenic effect, especially in females and with intravenous route. The expression of miR-29a was significantly diminished in intravenous (IV) and intramuscular (IM) groups at day 7, in both males and females. miR-29a may be responsible for the increased VEGF in the highest PEG-GNRs dose, but it is not responsible for the inhibited VEGF and PDGF levels in low PEG-GNRs doses. The study recommends the consideration of the critical role of dose, gender, and route of administration in PEG-GNRs pro-angiogenic activity, in medical applications as a direct cancer therapy and as a drug delivery agent.