Developing nature‐inspired nanomaterials with enzymatic activity is essential in combating bacterial biofilms. Here, it is reported that incorporating the carboxylic acid in phenolic/Fe nano‐networks can efficiently manipulate their peroxidase‐like activity via the acidic microenvironment and neighboring effect of the carboxyl group. The optimal gallic acid/Fe (GA/Fe) nano‐networks demonstrate highly enzymatic activity in catalyzing H2O2 into oxidative radicals, damaging the cell membrane and extracellular DNA in Streptococcus mutans biofilms. Theoretical calculation suggests that the neighboring carboxyl group can aid the H2O2 adsorption, free radical generation, and catalyst reactivation, resulting in superb catalytic efficiency. Further all‐atom simulation suggests the peroxidation of lipids can increase the cell membrane fluidity and permeability. Also, GA/Fe nano‐networks show great potential in inhibiting tooth decay and treating other biofilm‐associated diseases without affecting the commensal oral flora. This strategy provides a facile and scale‐up way to prepare the enzyme‐like materials and manipulate their enzymatic activity for biomedical applications.

Prodrug nanoassemblies combine the advantages of prodrug and nanomedicines, offering great potential in targeting the lesion sites and specific on-demand drug release, maximizing the therapeutic performance while minimizing their side effects. However, there is still lacking a facile pathway to prepare the lipid prodrug nanoassemblies (LPNAs). Herein, we report the LPNAs via the dynamic covalent boronate between catechol and boronic acid. The resulting LPNAs possess properties like drug loading in a dynamic covalent manner, charge reversal in an acidic microenvironment, and specific drug release at an acidic and/or oxidative microenvironment. Our methodology enables the encapsulation and delivery of three model drugs: ciprofloxacin, bortezomib, and miconazole. Moreover, the LPNAs are often more efficient in eradicating pathogens or cancer cells than their free counterparts, both in vitro and in vivo. Together, our LPNAs with intriguing properties may boost the development of drug delivery and facilitate their clinical applications.

To address the issue posed by drug-resistant bacteria and inspired by natural antimicrobial enzymes, we report the atomically doped copper on guanine-derived nanosheets (G–Cu) that possess the integrated catalytic cascade property of glucose oxidase and peroxidase, yielding free radicals to eliminate drug-resistant bacteria upon light irradiation. Density functional theory calculations demonstrate that copper could notably promote oxygen activation and H2O2 splitting on the G–Cu complexes. Further all-atom simulation and experimental data indicate that the lysis of bacteria is mainly induced by cell membrane damage and the elevation of intracellular reactive oxygen species. Lastly, the G–Cu complexes efficiently eliminate the staphylococci in the infected wounds and accelerate their closure in a murine model, with negligible side effects on the normal tissues. Therefore, our G–Cu complexes may provide an efficient nonantibiotic alternative to the current treatments for bacterial infections.

Vaginal candidiasis (VC) is a common disease of women and the main pathogen is Candida albicans (C. albicans). C. albicans infection incidence especially its drug resistance have become a global health threat due to the existence of C. albicans biofilms and the low bioavailability of traditional antifungal drugs. In recent years, nanomaterials have made great progresses in the field of antifungal applications. Some researchers have treated fungal infections with inorganic nanoparticles, represented by silver nanoparticles (AgNPs) with antifungal properties. Liposomes, polymeric nanoparticles, metal-organic frameworks (MOFs), and covalent organic frameworks (COFs) were also used to improve the bioavailability of antifungal drugs. Herein, we briefly introduced the recent developments on using above nanomaterials to combat C. albicans in antifungal applications.

The vagina has been regarded as a crucial route for drug delivery. Despite the wide range of available vaginal dosage forms for vaginal infection control, poor drug absorptivity remains a significant challenge due to various biological barriers in the vagina, such as mucus, epithelium, immune systems, and others. To overcome these barriers, different types of vaginal drug delivery systems (VDDSs), with outstanding mucoadhesive, mucus-penetrating properties, have been designed to enhance the absorptivity of vagina-administered agents in the past decades. In this Review, we introduce a general understanding of vaginal administration, its biological barriers, the commonly used VDDSs, such as nanoparticles and hydrogels, and their applications in controlling microbe-associated vaginal infections. Additionally, further challenges and concerns regarding the design of VDDSs will be discussed.