Novel nano-materials, RGD-tetrapeptide-modified 17β-amino-11α-hydroxyandrost-1,4-diene-3-one: synthesis, self-assembly based nano-images and in vivo anti-osteoporosis evaluation

Abstract

To find novel nano-materials with anti-osteoporosis activity and without side effects three novel anti-osteoporosis active amphiphiles, 17β-(RGD-AA-amido)-11α-hydroxyandrost-1,4-diene-3-one (5a: AA = Ser, 5b: AA = Val, 5c: AA = Phe), were constructed by coupling the bone resorption inhibiting active RGD-peptides and anti-osteoporosis active 17β-amino-11α-hydroxyandrost-1,4-diene-3-one. In the solid state 5a, 5b and 5c exist as dispersed globes of 300 nm–14 μm in diameter, dispersed eggs of 110 nm–19 μm in diameter and beads of 238 nm–22 μm in diameter, respectively. In ultrapure water 1.1 μM of 5a, 5b and 5c form nano-globes of 33–400 nm, 16–278 nm and 54–187 nm in diameter, respectively. At an oral dose of 110 nmol kg⁻¹5a–c effectively inhibited mice from developing osteoporosis. In contrast to estradiol, 5a–c did not induce mice to develop endometrial hyperplasia and thrombus.