Spermine-starch nanoparticles with antisense vicR suppress Streptococcus mutans cariogenicity.

Dental caries of permanent teeth is a common public health concern and has the second-highest incidence among global diseases. The exopolysaccharides (EPS) synthesized by Streptococcus mutans ( S. mutans ) are the principal virulence factor for cariogenic etiology. We previously discovered that an endogenous antisense vicR RNA (AS vicR ) could significantly inhibit EPS synthesis in S. mutans and reduce its cariogenicity. However, AS vicR cannot be directly applied in the oral environment. An appropriate vector is of great need to protect AS vicR from being degraded by nucleases for effective gene delivery to S. mutans . Functionally modified starches shed light on this field because of their excellent biocompatibility and biodegradability. In this study, a biocompatible and biodegradable spermine-starch nanocomposite (SSN) was constructed for AS vicR delivery. Starch was cationically functionalized by grafting endogenous spermine to closely bind with the recombinant AS vicR plasmid. The SSN not only protected the recombinant AS vicR plasmid from DNase I but also achieved highly efficient gene transformation to S. mutans via the hydrolysis of α-amylase in the saliva. In addition, SSN-AS vicR was shown to endow AS vicR with an increasing transformation efficiency approximately four times that of the naked AS vicR plasmid, as well as allowing for targeting specificity to the transcription of the vicR gene and the suppression of biofilm organization via EPS digestion. In particular, SSN-AS vicR nanoparticles exhibited excellent biological safety and maintained oral microbiota homeostasis in vivo. The SSN can be prepared in a ready-to-use formulation for targeting cariogenic bacteria, thus demonstrating important prospects in the prevention of dental caries.