## 1 Introduction  
Research in pharmaceutical and biomedicine faces the great challenge of increasing drug resistance, which endlessly forces the research community to implement new therapies [1]. In fact, resistant microbes with present medicines are weakly managed and constitute a major public health problem [2]. The oral cavity contains the habitat of numerous bacteria, whose synergy and interaction contributes to combat the invasion of external pathogens [3]. On the other hand, the human oral microbiome database (HOMD) reports more than 700 prokaryotic different species that coexist in the oral cavity that could negatively influence the health of human body and could also be involved in the progression of many infections and systemic pathologies [4]. Antibiotics are generally used to tackle the infectious states of the oral cavity, but recently the use of antimicrobial peptides (AMPs) is being considered. AMPs are a wide and diverse family of small amino acid peptides produced by the immune system of several species ranging from plant and animal kingdoms to all orders of life. AMPs play a protective function by establishing a defense system that may react in a fast and efficient manner [5]. They have a broad-spectrum activity against microorganisms, a low aptitude to induce resistance [6; 7], and are excellent candidates for clinical exploitation [8; 9]. However, only few AMPs have to date received the certification for entry into the market and for clinical use. Two lead examples are the magainin derivative (MSI-78), used as a topical cream for the treatment of foot infections in diabetes [10], and indolicidin (CP-226), used against severe acne and skin infections with _Staphylococcus aureus_ (_S. aureus_) resistant to methicillin [11]. AMPs mechanism of action is the disruption of the lipid bilayer integrity, leading to leakage of the intracellular content and death of the bacterium. AMPs are more specific and efficient than common antibiotics and are related to lower cell and tissue toxicity [12]. Nowadays, we know of more than 40 antimicrobial peptides in the oral cavity and many of these play a pivotal role in periodontal diseases as well as in orthodontics [13; 14]. On the other hand, thanks to their powerful antimicrobial activity, metal nanoparticles (NPs) have gained growing interest in the treatment of resistant pathogens. In this context, the combined use of AMPs and metal NPs seem to be very versatile since they hold the promise of interacting with different targets, therefore becoming of huge interest as an attractive alternative to antibiotics [15]. Moreover, microorganisms are unlikely to develop resistance against nanosystems, which attack multiple targets in the microbe. Together with AMPs, several metal NPs that represent a possible solution for the control of drug-resistant bacterial infections has also evolved [16; 17]. Among metal NPs, silver NPs (AgNPs) have received attention thanks to their potent broad spectrum antimicrobial activity. Since ancient times, the antimicrobial characteristics of silver have been studied and used for various purposes, primarily to improve tissue repair, fight infections, preserve drinking water, and prevent food spoilage. Silver use became less pronounced since the introduction of antibiotics. However, the recent influx of multidrug resistance it has become so potentially fatal that silver NPs have produced an astonishing return as an alternative or supplementary medication [18], opening up a whole pathway to new tools to combat a wide range of microorganisms [19; 20; 21; 22; 23]. The key to silver NPs broad and potent antibacterial activity is the multifaceted mechanism by which they have an effect on microbes. These mechanisms involve the disruption of ATP production and DNA replication due to gradual release of silver ions, the direct damage of cell membranes, and the generation of reactive oxygen species [24; 25; 26; 27; 28]. The mechanisms are likely to participate in their reported wide range of antimicrobial activity.