Demystifying Nanotherapeutic Modalities: Unravelling the Mysteries from Antibiofilm Mechanisms to Regenerative and Clinical Translation

Dental infections continue to pose a major health concern worldwide, driven by persistent microbial biofilms, dysregulated host responses, and suboptimal efficacy of conventional antimicrobial therapies. The emergence of nanotechnology has facilitated the development of therapeutic approaches that offer spatiotemporal, minimally invasive, and resistance-preventing alternatives for treating complex dental infections. This review critically assesses novel nanomaterial-based therapies designed to directly eradicate pathogenic microorganisms involved in periodontal disease, dental caries, oral candidiasis and endodontic infections. We first explore the roles of microbial dysbiosis and biofilm-associated pathogenicity as key factors in disease progression, thereby providing a biological rationale for targeted therapies. Particular emphasis is placed on pathogen-directed modalities such as photodynamic, photothermal, sonodynamic, chemodynamic, and nanozyme-based therapies, which allow localized microbial eradication while reducing antibiotic resistance. The design and effectiveness of multifunctional nanomaterials, ranging from bioactive nanoparticles and polymeric hydrogels to microsphere-based delivery systems and implant surface modifications, are analysed in the context of antimicrobial efficacy, biofilm disruption, and compatibility with regenerative processes. Meanwhile, recent advances in integration with tissue regeneration and the potential of artificial intelligence in diagnosis, treatment strategies and materials design are explored as complementary strategies that could improve therapeutic outcomes. By consolidating mechanistic and translational insights, this review highlights how pathogen-targeted nanotherapeutics are revolutionizing the treatment of dental infections with more effective and clinically viable solutions.