Four-armed host-defense peptidomimetics-augmented vanadium carbide MXene-based microneedle array for efficient photo-excited bacteria-killing

To explore the potential of vanadium compounds in disease treatment, a vanadium-based MXene composite nanosheet 4 [email protected]2C was constructed using a simple procedure by electrostatic coating a four-armed host-defense peptidomimetic 4 K10 on vanadium carbide (V2C) MXene. The two-dimensional therapeutics integrate membranolytic, photothermal, and photocatalytic abilities, realizing a great potential for efficient photo-excited bacteria-killing of focal infections via a microneedle-assisted approach. The proposed host-defense peptidomimetic augmenting MXene strategy achieves synergistic membranolytic-photothermal effects against biofilm bacteria by mediating high-selectivity bacteria binding, reducing bacteria heat resistance and increasing MXene-to-bacteria heat transfer efficiency. Moreover, the persistent photocatalytic disinfection and adjuvant effects of V2C degradation products on inhibiting bacterial rebound are highlighted. While the 4 [email protected]2C nanosheets demonstrate impressive in vitro antimicrobial activity with a ∼ 99.9996 % (5.5 log) reduction of methicillin-resistant Staphylococcus aureus (MRSA) and 100 % reduction of Pseudomonas aeruginosa at a low photothermal temperature of 54.1 °C, the dissolving microneedle system facilitates the transdermal delivery of 4 [email protected]2C nanosheets to eradicate skin infections with an efficacy superior to that of commercial Bactroban and with no significant in vivo toxicity. In a human ex vivo skin infection models, the 4 [email protected]2C nanosheets are highly efficacious in eradicating biofilm-associated infections with > 99.98 % (3.86 log) reduction in the skin MRSA burden.