# Treatment of Biofilm Communities: An Update on New Tools from the Nanosized World
## 1 Introduction  
The bell has tolled. Antimicrobial resistance is set to cause 30 million deaths by 2050 and will continue to cause a huge economic impact on health-care providers, around 100 Trillion USD$ [1]. The World Health Organization (WHO) has also recently outlined and ranked the microbes that should be highly prioritized for the development of new antibiotics [2]. These two documents highlight theextreme necessity of new therapies for microbial infection, claiming for research on the development of new antibiotics. Since the golden age of antibiotics, between 1940 and 1960, many different classes of molecules were discovered and introduced in clinical practice [3]. Right after introduction into clinics, specific antibiotic-resistant strains began to appear. From the 1970s, the development of new classes of antibiotics, i.e., completely different molecules compared to the ones already marketed, started to slow down, resulting in very few new antibacterial drugs introduced into practice. The last new antibiotic active against Gram-negative bacteria, quinolones, appeared in 1962. More recent is the availability of two new classes of drugs against Gram-positive bacteria. Lipopeptides and oxazolidinones were approved in 2000 and 2003, respectively [4]. Furthermore, the aforementioned rapid appearance of resistant strains terribly complicates the landscape. The generation of a new class of molecules requires at least a decade of work, whereas the onset of resistant isolates may take as fast as one or two years after introduction into clinics [5]. The problem of bacterial morbidity is especially prominent in implant-related or indwelling device-related infections, where bacteria stably colonize different types of implants, catheters or prosthetic valves. The colonization of these devices is mainly caused by the establishment of a biofilm, a bacterial community embedded in a self-produced Extracellular Polymeric Substance (EPS) that enables the microorganisms to settle at the site of infection and efficiently cope with various external potentially deleterious stresses [6]. This _milieu_ provides ideal conditions for bacteria to withstand antibiotic treatment, decreasing antibiotic efficacy due to lower penetration into deeper layers of the biofilm and the metabolic state of bacterial cells that is predominantly in the stationary phase. It is known that many antibiotics require an active bacterial proliferation, i.e., in the logarithmic phase. This condition is different from genetic resistance and is better referred to as tolerance [7] and it further intricates the landscape of bacterial infections. If examined together, these data highlight the need to complement the antimicrobial field with different preventive and therapeutic strategies that must be regarded with mounting interest. Indeed, the field of nanomedicine has emerged in the last decades as a promising option for new diagnostic and therapeutic alternatives in the clinic. Most clinical applications of nanotechnological discoveries involve non-infectious diseases, addressing mainly cancer [8]. Other fields of application include central nervous system diseases, cardiovascular and inflammatory pathologies. In addition, diagnostic and theranostic applications are also valued fields of investigation. It has to be mentioned that most of the research in this area is at a pre-clinical stage or undergoing clinical trials [8; 9]. The translation from bench-to-bed occurred mainly for cancer treatment. Since 1995, when Doxil(r), a liposomal-encapsulated form of doxorubicin to reduce its cardiotoxicity [10], earned the approval from the Federal Drug Administration (FDA), many other nano-drugs reached the clinics. The only example regarding infectious diseases is represented by AmBisome, a liposomal form of amphotericin B to treat fungal infections [11]. Therefore, the aim of this review is to summarize the state of the art regarding nanotechnological research in order to counteract biofilm communities.