Membrane interactions and cell selectivity of amphiphilic anticancer peptides

Following considerable research efforts on antimicrobial effects by cationic and amphiphilic peptides during the last couple of decades, increasing focus has recently been placed on additional host defense and other biological functions by such peptides, such as anti-inflammatory and anticancer effects. Regarding the latter, it has been increasingly understood that amphiphilic peptides present interesting opportunities not only for reaching selective cancer cell toxicity, but also for promoting uptake of other anticancer therapeutics and of nanopariculate delivery systems containing such drugs. While there is an emerging understanding of the direct antimicrobial function of amphiphilic peptides through bacterial membrane destabilization, the mechanisms underlying their anticancer effects remain less clear. Here, we therefore provide a brief overview on factors affecting toxicity of amphiphilic peptides against tumor and non-malignant cells, and also describe how such peptides can be combined with conjugation moieties or drug delivery systems for increased anticancer effects.