Targeted Eradication Of Streptococcus Mutans Via A Aptamer-Modified Nanosystem

This study aims to develop a novel aptamer-modified tetrahedral framework nucleic acid antimicrobial peptide to achieve the specific eradication of Streptococcus mutans, minimize adverse impact on oral microbiota, and mitigate the risk of antibiotic resistance. The tetrahedral framework nucleic acid (tFNA) was constructed through self-assembly of four single-stranded DNA sequences with complementary sticky ends, while the S. mutans-specific aptamer was attached by base pairing. The antimicrobial peptide, DIK1, was conjugated to tFNA via charge interaction. The drug loading efficiency was systematically evaluated at different ratios of tFNA and DIK1. The uptake and efficacy of the complex were investigated using fluorescence intensity, MIC, MTT, and CFU counting assays, while its antibacterial activity was assessed against multiple bacterial strains to validate the specificity. The selective bacterial eradication in co-culture bacterial model was examined through PMA-qPCR analysis and CFU counting. The modification of multiple aptamers significantly enhanced the uptake of Apt-tFNA@DIK1 by S. mutans, achieving a MIC of 8 µg/mL at a 4:1 ratio, superior to DIK1 alone. The complex demonstrated exceptional selectivity, reducing S. mutans CFU counts by over 95% in mono-cultures while leaving Enterococcus faecalis and Lactobacillus virtually unaffected, while PMA-qPCR and CFU counting validated its specificity in co-culture models. This novel Apt-tFNA@DIK1 nanosystem provides a precise and effective strategy for S. mutans eradication, enhancing therapeutic specificity while preserving microbiota balance and reducing resistance risks.