Inhibitory impact of a mesoporous silica nanoparticle-based drug delivery system on Porphyromonas gingivalis-induced bone resorption

Abstract

Controlling and reducing plaque formation plays a pivotal role in preventing and treating periodontal disease, often utilizing antibacterial drugs to enhance therapeutic outcomes. Mesoporous silica nanoparticles (MSN), an FDA-approved inorganic nanomaterial, possess robust physical and chemical properties, such as adjustable pore size and pore capacity, easy surface modification, and high biosafety. Numerous studies have exploited MSN to regulate drug release and facilitate targeted delivery. This study aimed to synthesize an MSN-tetracycline (MSN-TC) complex and investigate its inhibitory potential on Porphyromonas gingivalis (P. gingivalis)-induced bone resorption. The antibacterial efficacy of MSN-TC was evaluated through bacterial culture experiments. A P. gingivalis-induced bone resorption model was constructed by subcutaneously injecting P. gingivalis around the cranial bone of rats. Micro-computed tomography was employed to assess the inhibitory impact of MSN and MSN-TC on bone resorption. Furthermore, the influence of MSN and MSN-TC on osteoclast differentiation was examined in vitro. The MSN exhibited optimal pore size and particle dimensions for effective loading and gradual release of TC. MSN-TC demonstrated significant bacteriostatic activity against P. gingivalis. MSN-TC-treated rats showed significantly reduced cranial bone tissue destruction compared to MSN or TC-treated rats. Additionally, both MSN and MSN-TC exhibited inhibitory effects on the receptor activator of nuclear factor kappa-Β ligand-mediated osteoclast differentiation. The MSN-TC complex synthesized in this study demonstrated dual efficacy by exerting antibacterial effects on P. gingivalis and by resisting osteoclast differentiation, thereby mitigating bone resorption induced by P. gingivalis.

Fig. 1

Performance characterization of MSN. a FEG-SEM image of MSN, scale bar = 500 nm. b Transmission electron microscopy image of MSN, scale bar = 100 nm (Scale of local magnification = 50 nm). c MSN nitrogen adsorption-desorption isotherms. d MSN pore size distribution. e MSN particle size distribution. f MSN FTIR spectra. FEG-SEM field emission gun scanning electron microscopy

Fig. 2

TC loading and release trends. a Zeta-potentials of MSN, TC, and MSN-TC. b Total amount of TC loaded by MSN. c The cumulative percentage release of TC from MSN-TC. d Linear relationship of tetracycline concentration

Fig. 3

TC, MSN, and MSN-TC suppress RANKL-stimulated osteoclastogenesis from BMM. a Mature osteoclasts, labeled with TRAP staining, scale bar = 200 μm. b TRAP-positive multinucleated cells with multiple nuclei (three or more) were called osteoclasts and quantitatively analyzed in ratio to the total number of cells in the field of vision. **P < 0.01, *P < 0.05 vs. RANKL group

Fig. 4

TC, MSN, and MSN-TC inhibit RANKL-induced formation of the F-actin ring in osteoclasts. a The nucleus was labeled with blue DAPI and green Phalloidin-Ifluor™ 488 Conjugate F-actin ring, scale bar = 200 μm. b Cells with green F-actin were labeled as mature osteoclasts and quantitatively analyzed in percentage comparison with the number of mature osteoclasts in the RANKL group. ^**P < 0.01, ^*P < 0.05 ; ^####P < 0.0001, ^###P < 0.0009, ^##P < 0.01, ^#P < 0.05

Fig. 5

Reconstruction analysis of bone tissue in different experimental groups. Morphometric indices: a BV/TV, b Tb.N, c Tb.Sp, and d Tb.Th were analyzed by micro-CT. **P < 0.01, *P < 0.05 vs. control group; ^##P < 0.01, ^#P < 0.05 vs. Pg group

Fig. 6

Paraffin section of rat calvarial bone. a, b Calvarial bones are stained with HE and TRAP histology. c, d Osteoblasts and osteoclasts are quantified. **P < 0.01, ^*P < 0.05 vs. control group; ^##P < 0.01, ^#P < 0.05 vs. Pg group