Antibiotic resistance is a critical threat to humankind. If not addressed, bacterial resistances may lead to a return to a pre-antibiotic era, in which even minor infections could be fatal. Besides the immediate clinical impact, resistant pathogens severely complicate common medical interventions, such as surgeries or chemotherapy, where effective infection control is essential. The global spread of resistance is further aggravated by the slow development of new antibiotics, creating a widening gap between emerging resistances and therapeutic options. Combined with the high adaptability of bacteria and the decline in novel drug pipelines, this situation poses one of the most pressing challenges in modern medicine. In our group, we address these important issues through two different approaches:
1. Bacteria-Responsive Polymer Nanogels
With resistance rapidly spreading, few antibiotics of last resort remain viable and clinicians often rely on high doses of such drugs, which can cause severe side effects. Thus, multiple drugs are slowly vanishing from the clinics. To bring these drugs back to our arsenal, we aim to devlops stragies that delivery them more efficiently instead of modifying their molecualr structre like conventional drug-discovery strategies. For this, we devleop smart nanogels to deliver antibiotics selectively to infection sites by responding to the unique environment of resistant bacteria. The localized release boosts efficacy while minimizing systemic toxicity.
As triggers, we exploit bacterial enzymes, which resistant pathogens use as defense mechanisms. Instead of being inactivated by these enzymes, nanogels use them to cleave enzyme-sensitive linkers within the carrier, releasing encapsulated antibiotics directly at infection sites. This converts bacterial defenses into controlled, highly selective therapeutic triggers. Future studies will combine enzyme-triggered release with surface functionalization to enhance targeting, for example through glycopolymers that bind bacterial membranes.
2. Advanced Antimicrobial Polymers
Antimicrobial polymers (AMPs) act through membrane disruption, a mechanism that is less prone to resistance. Most current AMPs rely on quaternary ammonium salts, but these often cause toxicity such as hemolysis and can cause resistance formation. To overcome this, we are developing new AMPs based on sulfonium cations. Compared to traditional analogs, these materials may offer improved antibacterial potency with lower toxicity, while systematic studies of their structure-property relationships guide further optimization.