Alendronate and nanodiamonds (Alen-NDs) may have potential as therapeutic agents for osteoporosis by inducing osteogenic differentiation and potentially providing more bone-targeted drug delivery than oral osteoporosis medications, according to a study in Biomaterials Research.

Investigators synthesized Alen-NDs by forming an amide bond using DMTMM as a coupling reagent. They evaluated the cell viability of mouse fibroblast (NIH/3 T3) and mouse calvaria-derived preosteoblast (MC3T3-E1) cells after treatment of NDs and Alen-NDs. Osteogenic differentiation was confirmed by fluorescence-activated cell sorting (FACS) analysis.

The size of the NDs was 94.5±2.6 nm, and the size of the Alen-NDs was 118.8± 4.5 nm. No significant cytotoxicity was observed in all samples at a concentration <100 μg/ mL at 24 and 48 hours.


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In addition, no significant differences were found in proliferation rates of NIH/3 T3 cells between NDs and Alen-NDs in all concentrations, although treatment of NDs and Alen-NDs significantly reduced the proliferation rate of MC3T3-E1 cells. At a concentration of 100 μg/mL, NDs reduced the proliferation rate of MC3T3-E1 cells by 14.4% (4.2% and 9.0% reduction at concentrations of 10 μg/mL and 50 μg/mL, respectively) vs the untreated group. In comparison, Alen-NDs reduced the proliferation rate by 42.2% at a concentration of 100 μg/mL (11.7% and 22.0% reduction at concentrations of 10 μg/mL and 50 μg/mL, respectively) at 7 days.

MC3T3-E1 cells treated with NDs and Alen-NDs (100 μg/mL) demonstrated more changes in cuboidal shapes from a fibroblastic shape compared to the untreated group.

The higher differentiation of MC3T3-E1 cells treated by Alen-NDs vs the groups treated with osteogenic medium and NDs was confirmed by flow cytometry, alkaline phosphatase (ALP) activity, calcium deposition, and real-time polymerase chain reaction (RT-PCR).

“We successfully demonstrated the superior performance of Alen-NDs for osteogenic differentiation in terms of cell proliferation, morphological changes, FACS analysis, ALP activity, calcium contents, and messenger ribonucleic acid (mRNA) expression levels,” stated the investigators.

“We believe that Alen-NDs have great potential to enhance osteogenic differentiation, ultimately increasing bone formation,” the study authors added. “Our next goal will focus on the in vivo evaluation of Alen-NDs as a therapeutic agent for osteoporosis treatment.”

Reference

Ahn GY, Kim S-E, Yun TH, Choi I, Park D, Choi S-W. Enhanced osteogenic differentiation of alendronate-conjugated nanodiamonds for potential osteoporosis treatment. Biomater Res. 2021;25(1):28. doi:10.1186/s40824-021-00231-9