Pentapeptide-decorated silica nanoparticles loading salmon calcitonin for in vivo osteoporosis treatment with sustained hypocalcemic effect. (December 2019)

• Record Type: Journal Article
• Authors: Yu, P.; Chen, Y.; Wang, Y.; Liu, Y.; Zhang, P.; Guo, Q.; Li, S.; Xiao, H.; Xie, J.; Tan, H.; Li, J.
• Is Part Of: Materials today chemistry. Volume 14(2019)
• Publication Date: 2019-12
• Subjects: Peptide-modification -- Osteoporosis therapy -- SiO2 nanoparticles -- sCT -- Sustained release; Chemistry -- Periodicals; Materials -- Research -- Periodicals; Materials science -- Periodicals; Chemistry; Materials -- Research; Electronic journals; Periodicals; 660.282
• DOI: 10.1016/j.mtchem.2019.08.008
• Languages: English
• ISSNs: 2468-5194

Abstract

Abstract: Patients with osteoporosis are at a constant risk of bone fracture, and traditional treatment involves the administration of anabolic or antiresorptive drugs. At present, antiosteoporosis drugs, including salmon calcitonin (sCT), face many challenges such as short half-life and limited therapeutic efficiency to suppress bone loss and increase bone mass. Therefore, strategies to prolong the action time of antiosteoporosis drugs in vivo and improve their efficacy are essential. In this study, pentapeptide-decorated silica nanoparticles were synthesized and loaded with sCT (SiO2 -Pep@sCT) to improve the therapeutic efficiency. Cytotoxicity and proliferation tests confirmed that SiO2 -Pep@sCT had excellent biocompatibility. Biomarkers, including alkaline phosphatase activity, calcium flux, and calcified nodules, showed that SiO2 -Pep@sCT promoted osteogenic differentiation in osteoblasts. Further, in vivo evaluations revealed that SiO2 -Pep@sCT can efficiently prolong the half-life of sCT (from 30.5 to 69.3 min), leading to the maintenance of serum calcium in the normal physiological range in 48 h after single injection. For long-term treatment, micro-CT analysis showed that SiO2 -Pep@sCT can enhance trabeculation and accelerate the process of bone repair during osteoporosis. Thus, the SiO2 -Pep nanoparticle with uniform charge spatially distributed on the surface might be a potential drug/protein carrier for treating osteoporosis or other clinic diseases. Graphical abstract: Pentapeptide-decorated silica nanoparticles are capable of loading more salmon calcitonin (sCT) than unmodified ones. They can load and prolong the half-life of sCT (from 30.5 to 69.3 min) and maintain serum calcium levels in physical range for 48 h in vivo . Moreover, the sCT-loaded complex can also promote osteogenic differentiation of osteoblasts in vitro, further enhance trabeculation and accelerate bone-repair process with long-term osteoporosis therapy. Image 1 Highlights: We firstly fabricated the pentapeptide (GGGGD)-decorated silica nanoparticles with stronger negative charge. Pentapeptide decoration improved the performance of silica nanoparticels in loading and releasing salmon calcitonin. The prepared hybrid (SiO2 -Pep@sCT) promoted the proliferation and osteogenic differentiation of MC3T3-E1 cells. The complex exhibited extended half-life, sustainable sCT release and osteogenic capacity for osteoporosis therapy.