Abstract
Phototherapy has emerged to eradicate recalcitrant bacteria without causing drug resistance, but it is often accompanied by considerable limitations owing to a high tolerance of recalcitrant bacteria to heat and oxidative damage, leading to low efficiency of monotherapy and unwanted side effects. Assuming that employing antimicrobial peptides (AMPs) to disrupt bacterial membranes could reduce bacterial tolerance, a multifunctional "on-demand" nanosystem based on zeolitic imidazolate framework-8 (ZIF-8) with metal ions for intrinsic antibacterial activity was constructed to potently kill methicillin-resistant Staphylococcus aureus (MRSA). Then, microneedles (MNs) were used to transdermally deliver the ZIF-8-based nanosystem for localized skin infection. After MNs insertion, the nanoplatform could specifically deliver the loaded therapeutic components to bacterial infection sites through employing hyaluronic acid (HA) as a capping agent, thus realizing the "on-demand" payload release triggered by excess hyaluronidase secreted by MRSA. The prepared nanosystem and MNs were confirmed to exert an amplified triple therapy originating from membranolytic effect, phototherapy, and ion therapy, thus displaying a powerful bactericidal and MRSA biofilm destruction ability. This intelligent antimicrobial strategy may bring a dawn of hope for eradicating multidrug-resistant bacteria and biofilms.