Amphiphilic dendrimers against antibiotic resistance: light at the end of the tunnel?
Résumé
The alarming and prevailing antimicrobial resistance (AMR) calls urgently for novel antibacterial agents that are effective and stable but do not induce resistance development. Amphiphilic dendrimers are emerging as a promising new paradigm to combat AMR, because they can mimic the antimicrobial peptides with potent antibacterial activity and low likelihood of generating resistance, while being stable against enzymatic degradation thanks to the unique dendritic architecture. Importantly, these amphiphilic dendrimers are composed of distinct hydrophobic and hydrophilic entities bearing dendritic structures, which can be precisely designed and synthesized for optimal hydrophobic-hydrophilic balance to yield potent antibacterial activity with minimizing adverse effect and drug resistance. In this short review, we present the challenges and current state of research in developing amphiphilic dendrimers as new antibiotic substitutes. We start with a brief overview of the advantages and opportunities associated with using amphiphilic dendrimers to combat AMR. We then outline the specific considerations and the mechanisms underlying the antibacterial activity of amphiphilic dendrimers. We focus on the importance of the amphiphilic nature of a dendrimer that balances hydrophobicity and hydrophilicity via gauging the hydrophobic entity and the dendrimer generation, branching unit, terminal group and charge for high antibacterial potency and selectivity while minimizing toxicity. Finally, we present the future challenges and perspectives in amphiphilic dendrimers as antibacterial candidates for combating AMR.
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