Synthesis of Hydrogen-Bonded Organic Framework Nanoenzyme for Targeting Antibacterial Applications

Bacterial infection poses a significant hazard to public health and life. Antibiotic therapy can readily result in multidrug resistance. Despite significant efforts to enhance the effectiveness of current antibiotics or create new ones， bacteria's innate capacity to develop resistance has outpaced the rate of antibiotic development. This suggests that attempts to create sustainable antimicrobial treatments are ultimately destined to be unsuccessful. Herein， a selective therapeutic HOFzyme （Pro@HOF@apt-Cu） based on DNA-templated ultrasmall CuNPs grafted on peroxidase-mimicking FeTCPP-based HOF targeting lipopolysaccharide （LPS） is presented. FeTCPP-based HOF exhibit excellent POD-like activity， being not only able to catalyze the generation of more toxic hydroxyl radicals from H2O2 in the infection-rich microenvironment to disrupt the bacterial periplasm， but also able to oxidize surface Cu（0） to Cu（Ⅰ）， thus boosting the bioorthogonal catalytic activity. The conjugation of the HOF with aptamer allows for active targeting of LPS on the surface of gram-negative bacteria. The antibacterial action of these HOFzymes is observably more significant than non-targeted treatment. Moreover， the inherent pores of HOF facilitated the loading of prodrugs， which realized effective drug delivery and in situ synthesis， greatly reduced off-target toxicity and enhanced therapeutic effects. Overall， this synergistic therapeutic strategy shows promising potential as a future treatment for infections caused by gram-negative bacteria.