Introduction

In recent years, the field of nanomedicine has seen a burgeoning interest in mesoporous silica nanoparticles (MSNs) as innovative therapeutic carriers. MSNs are celebrated for their ability to deliver a wide range of drugs to targeted areas within the body, significantly reducing systemic toxicity and improving drug solubility. Distinguished by tunable morphologies, high surface areas, large pore volumes, and ease of functionalization, MSNs have emerged as superior drug delivery platforms compared to other nanocarriers. This article delves into the applications of MSNs in oral therapeutics, particularly in the treatment of dental caries, dentin hypersensitivity, periodontitis, endodontic treatment failure, maxillofacial space infections, oral squamous cell carcinoma, and bone regeneration.  

Fig. 1 Mesoporous silica nanoparticle (MSN) as a vehicle for drugs (Fang L., et al. 2023).

Mesoporous Silica Nanoparticles as Vehicles for Oral Drugs

Chlorhexidine

Chlorhexidine (CHX) has long been the gold standard for antibacterial agents due to its effectiveness against a broad spectrum of bacteria and fungi. Incorporating CHX into MSNs (CHX@MSNs) enhances its antibiofilm efficiency and prolongs its antibacterial activity. When used in dental applications, such as dentin adhesives and restorative materials, CHX@MSNs demonstrated sustained release properties, reducing bacterial resistance and enhancing mechanical performance. This dual functionality positions CHX@MSNs as an advanced solution for oral antibacterial therapies.

Silver Nanoparticles

Silver nanoparticles (AgNPs) are renowned for their antimicrobial properties. However, direct incorporation into dental materials often results in aggregation and cytotoxicity. MSNs serve as an effective nanocarrier for AgNPs, providing controlled release and preventing aggregation. Studies have demonstrated that Ag-MSNs incorporated into polymethylmethacrylate (PMMA) maintain sustained antibacterial activity and mechanical strength, offering a promising approach for applications such as dentures and orthodontic adhesives. Additionally, Ag-MSNs combined with remineralization agents have shown potential in treating dentin hypersensitivity by occluding dentinal tubules and preventing bacterial growth.

Quaternary Ammonium Salts

Quaternary ammonium salts (QASs) exhibit potent antibacterial activity by disrupting bacterial cell membranes. Despite their effectiveness, their activity is limited by a requirement for direct contact with bacteria. MSNs enhance the efficacy of QASs by enabling the co-delivery of multiple agents, thereby overcoming these limitations. Ag/QAS-MSNs have shown significant promise in treating head and neck cancers (HNCAs) by providing sustained antibacterial and anticancer activity. This highlights the potential of MSNs in co-delivering QASs with other therapeutic agents to manage complex oral conditions.

Curcumin

Curcumin, noted for its antibiofilm, anti-inflammatory, and antitumor activities, suffers from poor water solubility and bioavailability. Loading curcumin into MSNs (Cur-MSNs) addresses these challenges by enhancing its stability and providing controlled release. Studies have showcased Cur-MSNs' effectiveness in reducing biofilm formation and combating tumor growth, both in vitro and in vivo. This makes Cur-MSNs a versatile therapeutic option for infections and cancer therapy within the oral cavity.

Applications of MSNs in Stomatology

Dental Caries

S. mutans plays a pivotal role in the formation of dental caries by generating an acidic environment conducive to tooth demineralization. CHX@MSNs have exhibited prolonged and responsive release, targeting the acidic environment produced by S. mutans to curb biofilm formation and inhibit caries. Additionally, experimental dental composites and adhesives containing CHX@MSNs have demonstrated outstanding inhibitory effects on biofilm growth, maintaining their mechanical integrity and extending the longevity of dental restorations.

Dentin Hypersensitivity

Dentin hypersensitivity is primarily caused by the exposure of dentinal tubules due to abrasion, erosion, or gingival recession. MSNs loaded with nanohydroxyapatite (nHAp@MSN) have shown potential in occluding exposed tubules, offering relief from hypersensitivity. Additionally, bioactive glass nanoparticles (BGNs) incorporated into MSNs (Ag-BGNs@MSNs) induced dentinal tubule occlusion and exhibited antibacterial properties. These advancements underscore the potential of MSN-based biomaterials in treating dentin hypersensitivity effectively.

Periodontitis

Periodontitis, a destructive inflammatory condition affecting the supporting structures of teeth, often requires robust antibacterial and anti-inflammatory treatments. MSNs loaded with antibiotics or anti-inflammatory agents such as resveratrol have demonstrated significant therapeutic potential. The stimuli-responsive release of these agents from MSNs targets the periodontal tissue, enhancing drug concentration at the site of infection and promoting osteogenesis. MSN-based therapies, therefore, offer a multifaceted approach to managing periodontitis by addressing both microbial and inflammatory components.

Endodontic Treatment Failure

Persistent infections, improperly cleaned root canals, and untreated secondary canals contribute to endodontic treatment failure. Enterococcus faecalis is notably resistant to conventional endodontic treatments. MSN-based sonodynamic therapy (SDT), utilizing ultrasound to activate sonosensitizers and generate reactive oxygen species (ROS), presents a novel method to eradicate E. faecalis effectively. MSNs conjugated with sonosensitizers like protoporphyrin IX (PpIX) and Fe ions (MSNs@P-Fe) demonstrated superior antibacterial efficacy, underscoring the potential of MSN-based platforms in improving endodontic outcomes.

Maxillofacial Space Infection

Maxillofacial infections, often stemming from odontogenic causes, necessitate effective antibacterial strategies. Selenium (Se) nanoparticles incorporated into MSNs (Se-MSNs) displayed enhanced antibacterial activity against Staphylococcus aureus, a common pathogen in such infections. Additionally, MSN-based carriers loaded with antibiotics and enzymes showed potential in penetrating biofilms, providing a targeted approach to managing complex maxillofacial infections.

Oral Squamous Cell Carcinoma (OSCC)

Treatment of OSCC requires precise targeting of tumor cells while minimizing damage to surrounding healthy tissues. MSNs' responsiveness to pH and thermal changes in the tumor microenvironment allows for the selective delivery of anticancer agents like paclitaxel (PTX) and 5-fluorouracil (5-FU). Studies have demonstrated that MSNs co-delivering glucose oxidase (GOx) and PTX disrupt the tumor's energy supply, enhancing anticancer efficacy. Additionally, 5-FU-loaded MSNs (MSN-5-FU) provide sustained release, reducing the side effects commonly associated with systemic chemotherapy.

Regeneration in the Oromaxillofacial Region

Bone defects resulting from periodontitis, infections, or tumors necessitate effective regenerative solutions. MSNs, modified with osteogenic peptides or loaded with bone morphogenetic protein-2 (BMP-2), have shown remarkable potential in promoting osteogenesis. By facilitating the slow release of osteogenic factors and supporting the differentiation of mesenchymal stem cells (MSCs), MSN-based platforms offer promising solutions for bone regeneration in maxillofacial applications.

Conclusion

Mesoporous silica nanoparticles (MSNs) present an exciting frontier in the field of oral therapeutics. Their inherent properties, including high drug loading capacity, tunable release profiles, and ease of customization, make them highly suitable for a range of applications in stomatology. MSNs have demonstrated significant potential in improving the efficacy of antibiofilm therapies, cancer treatments, and bone regeneration strategies, highlighting their versatility.

However, several challenges must be addressed to fully realize the clinical potential of MSNs. Cytotoxicity induced by oxidative stress and residual drug retention within MSNs poses notable concerns. Moreover, scaling up the synthesis of MSNs while maintaining consistency and functionality remains a significant hurdle.

Despite these challenges, the prospects of MSNs in oral therapeutics are immensely promising. With continued research and development, MSN-based formulations could revolutionize the treatment of various oral diseases, offering safer, more effective, and targeted therapeutic options. The convergence of material science, nanotechnology, and medicine will undoubtedly propel MSNs to the forefront of innovative oral healthcare in the future.