Background: Enterococcus faecalis has emerged as a predominant endodontic pathogen due to its high isolation rate in endodontic failure cases, remarkable biofilm-forming capacity, and inherent resistance to conventional therapies. Recent advances in nanocarrierassisted antimicrobial photodynamic therapy (Nano-aPDT) have introduced a novel disinfection paradigm, demonstrating promising potential in eradicating persistent root canal infections through three key mechanisms: enhanced photosensitizer stability, improved targeted delivery, and optimized reactive oxygen species (ROS) generation.

Objectives: This systematic review and meta-analysis was designed to: comprehensively evaluate the antimicrobial efficacy of nanocarrier-assisted photodynamic therapy (Nano-aPDT) against Enterococcus faecalis biofilms; conduct comparative effectiveness analyses between Nano-aPDT and standard interventions including sodium hypochlorite (NaOCl) irrigation and conventional photodynamic therapy (PDT); critically appraise the therapeutic advantages and technical limitations of Nano-aPDT as an endodontic disinfection strategy; and synthesize evidence-based recommendations to facilitate clinical translation of this emerging technology.

Methods: The study protocol received prospective registration in PROSPERO (CRD420251068155) and was executed in strict compliance with PRISMA reporting standards. An exhaustive systematic search was conducted spanning PubMed, Embase, Web of Science, Scopus, and the Cochrane Library through June 1, 2025. Methodological rigor was evaluated utilizing the Cochrane Risk of Bias assessment instrument. Quantitative synthesis was undertaken employing RevMan 5.4 statistical software, utilizing risk ratios (RR) accompanied by 95% confidence intervals (CI) as principal effect size metrics, implemented via the Mantel-Haenszel randomeffects modeling approach. Between-study heterogeneity was rigorously assessed through I² statistical measures.

Results: The final analysis included nine rigorously screened studies, comprising eleven independent datasets comparing Nano-aPDT versus NaOCl and nine datasets evaluating Nano-aPDT against conventional PDT. Meta-analysis revealed two key findings: First, Nano-aPDT showed statistically significant but modestly reduced antibacterial efficacy relative to NaOCl (pooled RR = 0.85, 95% CI: 0.74–0.97, p = 0.01). Second, Nano-aPDT demonstrated substantially greater bactericidal activity compared to conventional PDT (pooled RR = 1.33, 95% CI: 1.11–1.78, p = 0.004).

Both comparisons exhibited substantial heterogeneity (I²=99%), indicating notable variations across studies in experimental design, treatment parameters, and outcome assessment. Most studies carried moderate risk of bias, primarily due to: Suboptimal randomization methodologies; Inadequate allocation concealment; Lack of blinding implementation; Incomplete reporting of analytical approaches.

Conclusions: In vitro evidence indicates that nanocarrier-assisted antimicrobial photodynamic therapy (Nano-aPDT) achieves significantly greater bactericidal activity against Enterococcus faecalis than conventional PDT, although its efficacy remains slightly lower than that of NaOCl.