Dendrimers as Multi-Target Nanotherapeutic Strategies Against Antimicrobial Resistance: Current Drug Targets and Mechanistic Insights
TL;DR
Dendrimers, synthetic, highly branched nanostructures with well-defined architecture and tunable surface functionality, have come as promising multi-target antimicrobial systems that allow dendrimers to overcome multiple bacterial resistance mechanisms simultaneously.
Abstract
Antibiotics are also regarded as transformative therapeutic agents that are rapidly losing their clinical effectiveness because of the global escalation of antimicrobial resistance (AMR). Irrational and extensive antibiotic use has accelerated the emergence of resistant pathogens through mechanisms such as low membrane permeability, target modification, active efflux, quorum–sensing–regulated virulence, and biofilm formation, which leads to increased morbidity and mortality worldwide. This urgent crisis needs innovative, target-based therapeutic techniques beyond conventional antibiotics. In this context, dendrimers, synthetic, highly branched nanostructures with well-defined architecture and tunable surface functionality, have come as promising multi-target antimicrobial systems. Dendrimers directly disrupt bacterial cell membranes, which enhances permeability and promotes antibiotic penetration while simultaneously interacting with critical resistance determinants, including penicillin-binding proteins (PBPs), quorum sensing (QS) pathways, which are involved in virulence and biofilm regulation, and efflux pumps responsible for drug expulsion. Multiple dendrimer classes, which include poly (amid amine) (PAMAM), polypropylene imine (PPI), carbosilane, and peptide dendrimers, have shown intrinsic antimicrobial activity and strong synergistic effects with conventional antibiotics. Their internal cavities enable efficient drug encapsulation, and surface modifications allow targeted delivery, improved pharmacokinetics, and enhanced activity against both planktonic bacteria and biofilms. These properties allow dendrimers to overcome multiple bacterial resistance mechanisms simultaneously. This review gives a focus on the antimicrobial mechanisms, dendrimer design parameters, and pharmaceutical approaches that allow them to be translated into next-generation anti-infective treatments