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With the increased emergence and threat of multi-drug resistant microorganisms, MXenes have become not only an emerging class of two-dimensional functional nanomaterials, but also potential nanomedicines (i.e., antimicrobial agents) that deserve further exploration. Very recently, Ti 3 C 2 MXene was observed to offer a unique membrane-disruption effect and superior light-to-heat conversion efficiency, but its antibacterial property remains unsatisfactory due to poor MXene-bacteria interactions, low photothermal therapy efficiency, and occurrence of bacterial rebound in vivo. Herein, the cationic antibiotic ciprofloxacin (Cip) is combined with Ti 3 C 2 MXene, and a hybrid hydrogel was constructed by incorporating Cip-Ti 3 C 2 nanocomposites into the network structure of a Cip-loaded hydrogels to effectively trap and kill bacteria. We found that the Cip-Ti 3 C 2 nanocomposites achieved an impressive in vitro bactericidal efficiency of >99.99999% (7.03 log 10 ) for the inhibition of methicillin-resistant Staphylococcus aureus (MRSA) by combining chemotherapy with photothermal therapy. In an MRSA-induced murine abscess model, the hybrid hydrogel simultaneously achieved high-efficiency sterilization and long-term inhibition effects, avoiding the rebound of bacteria after photothermal therapy, and thus maximized the in vivo therapeutic efficacy of Ti 3 C 2 MXene-based systems. Overall, this work provides a strategy for efficiently combating localized bacterial infection by rationally designing MXene-based hybrid hydrogels. STATEMENT OF SIGNIFICANCE: Two-dimensional Ti 3 C 2 MXene was recently regarded as a promising functional nanomaterial, however, its antibacterial applications are limited by the poor MXene-bacteria interactions, low photothermal therapy efficiency, and the occurrence of bacterial rebound in vivo. This work aims to construct a Ti 3 C 2 MXene-based hybrid hydrogel for chemo-photothermal therapy and enhance the antimicrobial performance via a combination of the high-efficiency sterilization of ciprofloxacin-Ti 3 C 2 nanocomposites with the long-term inhibition effect of ciprofloxacin hydrogel. The present study provides an example of efficient MXene-based antimicrobials to treat localized bacterial infection such as methicillin-resistant Staphylococcus aureus (MRSA)-induced skin abscess., Competing Interests: Declaration of Competing Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022. Published by Elsevier Ltd.)

Membrane-disruptive peptides/peptidomimetics (MDPs) are antimicrobials or anticarcinogens that present a general killing mechanism through the physical disruption of cell membranes, in contrast to conventional chemotherapeutic drugs, which act on precise targets such as DNA or specific enzymes. Owing to their rapid action, broad-spectrum activity, and mechanisms of action that potentially hinder the development of resistance, MDPs have been increasingly considered as future therapeutics in the drug-resistant era. Recently, growing experimental evidence has demonstrated that MDPs can also be utilized as adjuvants to enhance the therapeutic effects of other agents. In this review, we evaluate the literature around the broad-spectrum antimicrobial properties and anticancer activity of MDPs, and summarize the current development and mechanisms of MDPs alone or in combination with other agents. Notably, this review highlights recent advances in the design of various MDP-based drug delivery systems that can improve the therapeutic effect of MDPs, minimize side effects, and promote the co-delivery of multiple chemotherapeutics, for more efficient antimicrobial and anticancer therapy., Competing Interests: The authors declare no conflict of interest., (© 2021 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.)