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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.

The development of colitis-associated colorectal cancer is known to be associated with the inflammation-dysplasia-carcinoma pathway, and thus, chronic inflammation represents an inducer and promoter of cancer. To inhibit the evolution from colitis to colorectal cancer and provide an efficient anticancer therapy, a surface-engineered vanadium carbide MXene nanoenzyme (MXenzyme) is developed with both amino functionalization and gallium doping (Ga/V 2 C-NH 2 ). Benefiting from multiple enzymemimicking activities, MXenzymes have shown great potential to decrease excessive reactive oxygen species and inhibit the levels of proinflammatory cytokines, resulting in good anti-inflammatory effects on dextran sulfate sodium-induced acute colitis. Moreover, the gallium-doped MXene with an amino-functionalized surface can mediate improved MXene-tumor interactions and inhibitory effects on cell proliferation, achieving precise and efficient chemo-photothermal therapy. Elemental doping into MXene is also highlighted as a feasible strategy to achieve the loading and controlled release of gallium. As a result, complete tumor ablation without further recurrence is observed for the colon cancer-bearing mice that receive Ga/V 2 C-NH 2 and near infrared irradiation, while the MXenzyme system displays excellent biocompatibility at both the cellular and animal levels. These findings not only enrich the research of MXene, but also illustrate its efficient therapeutic promise in anti-inflammation and photoenhanced antitumor therapy of colon diseases.

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