Antimicrobial Peptides and Cationic Nanoparticles: A Broad-Spectrum Weapon to Fight Multi-Drug Resistance Not Only in Bacteria

Abstract

In the last few years, antibiotic resistance and, analogously, anticancer drug resistance have increased considerably, becoming one of the main public health problems. For this reason, it is crucial to find therapeutic strategies able to counteract the onset of multi-drug resistance (MDR). In this review, a critical overview of the innovative tools available today to fight MDR is reported. In this direction, the use of membrane-disruptive peptides/peptidomimetics (MDPs), such as antimicrobial peptides (AMPs), has received particular attention, due to their high selectivity and to their limited side effects. Moreover, similarities between bacteria and cancer cells are herein reported and the hypothesis of the possible use of AMPs also in anticancer therapies is discussed. However, it is important to take into account the limitations that could negatively impact clinical application and, in particular, the need for an efficient delivery system. In this regard, the use of nanoparticles (NPs) is proposed as a potential strategy to improve therapy; moreover, among polymeric NPs, cationic ones are emerging as promising tools able to fight the onset of MDR both in bacteria and in cancer cells.

Keywords: antibiotics; anticancer drugs; antimicrobial peptides; cationic nanoparticles; multi-drug resistance.

Figure 1

Comparison among membrane lipid composition of healthy mammalian cells, Gram-positive and Gram-negative bacteria.

Figure 2

Comparison among membrane lipid composition of healthy mammalian cells and cancer cells.

Figure 3

Models of ACPs’ action. In the carpet model (left), ACPs bind to the cell membrane via electrostatic interactions and, subsequently, ACPs may enter the cell membrane, inducing membrane disruption. In the barrel-stave model (right), peptides self-aggregate and form a transmembrane pore, leading to membrane depolarization.

Figure 4

NPs’ interaction with cell membrane and their killing ability on cancer cells and bacteria.