From Nanobiotechnology, Positively Charged Biomimetic Dendrimers as Novel Antibacterial Agents: A Review

Abstract

The alarming increase in antimicrobial resistance, based on the built-in abilities of bacteria to nullify the activity of current antibiotics, leaves a growing number of bacterial infections untreatable. An appealing approach, advanced in recent decades, concerns the development of novel agents able to interact with the external layers of bacteria, causing irreparable damage. Regarding this, some natural cationic antimicrobial peptides (CAMPs) have been reconsidered, and synthetic cationic polymers, mimicking CAMPs and able to kill bacteria by non-specific detrimental interaction with the negative bacterial membranes, have been proposed as promising solutions. Lately, also dendrimers were considered suitable macromolecules for the preparation of more advanced cationic biomimetic nanoparticles, able to harmonize the typical properties of dendrimers, including nanosize, mono-dispersion, long-term stability, high functionality, and the non-specific mechanism of action of CAMPs. Although cationic dendrimers are extensively applied in nanomedicine for drug or gene delivery, their application as antimicrobial agents is still in its infancy. The state of the art of their potential applications in this important field has therefore been reviewed here, with particular attention to the innovative case studies in the literature including also amino acid-modified polyester-based dendrimers, practically unexplored as membrane-active antimicrobials and able to kill bacteria on contact.

Keywords: amino acid-modified polyester-based dendrimers; antibiotic resistance; biomimetic cationic dendrimer nanoparticles; cationic antimicrobial polymers; non-specific membrane disruption; novel antimicrobial agents.

Figure 1

Number of publications as a function of time, obtained by typing the key words “antimicrobial dendrimers” in Scopus.

Figure 2

Number of publications, as a function of time, obtained by typing the key phrase “antimicrobial dendrimers” in Scopus (purple bars) and that obtained by typing “cationic antibacterial dendrimers” (yellow bars), topic of the review.

Figure 3

CADs developed in recent decades.

Figure 4

Bacterial species employed to evaluate the antibacterial activity of cationic Ds.

Figure 5

Antibacterial activity of the best performing compounds for one structural category of CADs against P. areruginosa.

Figure 6

Percentage of the main classes of CADs developed in the years 2010–2020.

Figure 7

Percentages of the main biological investigations conducted on CADs developed in the years 2010–2020.