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Bacteria-derived hydrogen sulfide (H 2 S) often contributes to the emergence of antibiotic-recalcitrant bacteria, especially persister (a sub-population of dormant bacteria), thus causing the treatment failure of Catheter-associated urinary tract infection (CAUTI). Here, an H 2 S harvester nanosystem to prevent the generation of persister bacteria and disrupt the dense biofilm matrix by the self-adaptive ability of shape-morphing is prepared. The nanosystem possesses a core-shell structure that is composed of liquid metal nanoparticle (LM NP), AgNPs, and immobilized urease. The nanosystem decomposes urea contained in urine to generate ammonia for eliminating bacteria-derived H 2 S. Depending on the oxidative layer of liquid metal, the nanosystem also constitutes a long-lasting reservoir for temporarily storing bacteria-derived H 2 S, when urease transiently overloads or in the absence of urine in a catheter. Depriving H 2 S can prevent the emergence of persistent bacteria, enhancing the bacteria-killing efficiency of Ga 3+ and Ag + ions. Even when the biofilm has formed, the urine flow provides heat to trigger shape morphing of the LM NP, tearing the biofilm matrix. Collectively, this strategy can turn trash (urea) into treasure (H 2 S scavengers and biofilm rippers), and provides a new direction for the antibacterial materials application in the medical field., (© 2024 Wiley‐VCH GmbH.)

Macrophages are the primary effectors against potential pathogen infections. They can be "parasitized" by intracellular bacteria, serving as "accomplices", protecting intracellular bacteria and even switching them to persisters. Here, using a freeze-thaw strategy-based microfluidic chip, a "Themis" nanocomplex (TNC) is created. The TNC consists of Lactobacillus reuteri-derived membrane vesicles, heme, and vancomycin, which cleaned infected macrophages and enhanced uninfected macrophages. In infected macrophages, TNC releases heme that led to the reconstruction of the respiratory chain complexes of intracellular persisters, forcing them to regrow. The revived bacteria produces virulence factors that destroyed host macrophages (accomplices), thereby being externalized and becoming vulnerable to immune responses. In uninfected macrophages, TNC upregulates the TCA cycle and oxidative phosphorylation (OXPHOS), contributing to immunoenhancement. The combined effect of TNC of cleaning the accomplice (infected macrophages) and reinforcing uninfected macrophages provides a promising strategy for intracellular bacterial therapy., (© 2024 Wiley‐VCH GmbH.)

Wound healing is a well-orchestrated progress associated with angiogenesis, epithelialization, inflammatory status, and infection control, whereas these processes are seriously disturbed in diabetic wounds. In this study, a biohybrid dressing integrating the inherent ability of Bromeliad leaf (photosynthesis and self-draining) with the therapeutic effect of artificial materials (glucose-degrading and ROS-scavenging) is presented. The dressing consists of double-layered structures as follows: 1) Outer layer, a Bromeliad leaf substrate full of alginate hydrogel-immobilized glucose oxidase (GOx@Alg@Bromeliad substrate, abbreviated as BGA), can generate oxygen to guarantee the GOx-catalyzed glucose oxidation by photosynthesis, reducing local hyperglycemia to stabilize hypoxia inducible factor-1 alpha (HIF-1α) for angiogenesis and producing hydrogen peroxide for killing bacteria on the surface of wound tissue. The sophisticated structure of the leaf drains excessive exudate away via transpiration-mimicking, preventing skin maceration and impeding bacterial growth. 2) Inner layer, microneedles containing catalase (CAT-HA MNs, abbreviated as CHM), reduces excessive oxidative stress in the tissue to promote the proliferation of fibroblasts and inhibits proinflammatory polarization of macrophages, improving re-epithelialization of diabetic wounds. Together, the biohybrid dressing (BGA-CHM, abbreviated as BCHM) can enhance angiogenesis, strengthen re-epithelialization, alleviate chronic inflammation, and suppress bacterial infection, providing a promising strategy for diabetic wound therapy., (© 2023 Wiley-VCH GmbH.)

Controlling phosphorylation processes of proteins is a facile way for manipulating cell fates. Herein, a synergistic therapeutic strategy utilizing a near-infrared (NIR)-responsive nanocatalyst (NC) complex is presented, which is comprised of photoactive NC and protein phosphatase 2A (PP2A), to synergistically inhibit hyperphosphorylation of mitogen-activated protein kinase (MAPK) pathway for cancer therapy, as an example of many biological processes this approach can apply to. NIR-triggered release of PP2A specially dephosphorylates and inactivates mitogen-activated protein kinase kinase (MAP2K, also known as MEK) and extracellular regulated protein kinases (ERK) in the MAPK pathway, meanwhile, the NIR-triggered activation of NC decreases the level of intracellular adenosine triphosphate to attenuate protein phosphorylation of MEK and ERK. The synergistic therapeutics effectively suppress melanoma progression by inhibiting hyperphosphorylation of the MAPK pathway. In addition, the nanocatalyst complex reduces the risk of drug-resistance through inhibiting a rebound of RAS-GTP. The NIR-responsive nanocatalyst complex paves a novel way for cancer therapeutics., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

CRISPR/Cas9 system is a powerful toolbox for gene editing. However, the low delivery efficiency is still a big hurdle impeding its applications. Herein, we report a strategy to deliver Cas9-sgPlk-1 plasmids (CP) by a multifunctional vehicle for tumor therapy. We condensed CPs on TAT peptide-modified Au nanoparticles (AuNPs/CP, ACP) via electrostatic interactions, and coated lipids (DOTAP, DOPE, cholesterol, PEG2000-DSPE) on the ACP to form lipid-encapsulated, AuNPs-condensed CP (LACP). LACP can enter tumor cells and release CP into the cytosol by laser-triggered thermo-effects of the AuNPs; the CP can enter nuclei by TAT guidance, enabling effective knock-outs of target gene (Plk-1) of tumor (melanoma) and inhibition of the tumor both in vitro and in vivo. This AuNPs-condensed, lipid-encapsulated, and laser-controlled delivery system provides a versatile method for high efficiency CRISPR/Cas9 delivery and targeted gene editing for treatment of a wide spectrum of diseases., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The type II bacterial clustered, regularly interspaced, short palindromic repeats (CRISPR)-Cas9 (CRISPR-associated protein) system (CRISPR-Cas9) is a powerful toolbox for gene-editing, however, the nonviral delivery of CRISPR-Cas9 to cells or tissues remains a key challenge. This paper reports a strategy to deliver Cas9 protein and single guide RNA (sgRNA) plasmid by a nanocarrier with a core of gold nanoclusters (GNs) and a shell of lipids. By modifying the GNs with HIV-1-transactivator of transcription peptide, the cargo (Cas9/sgRNA) can be delivered into cell nuclei. This strategy is utilized to treat melanoma by designing sgRNA targeting Polo-like kinase-1 ( Plk1 ) of the tumor. The nanoparticle (polyethylene glycol-lipid/GNs/Cas9 protein/sgPlk1 plasmid, LGCP) leads to >70% down-regulation of Plk1 protein expression of A375 cells in vitro. Moreover, the LGCP suppresses melanoma progress by 75% on mice. Thus, this strategy can deliver protein-nucleic acid hybrid agents for gene therapy.

Bacterial infections, especially multidrug-resistant bacterial infections, are an increasingly serious problem in the field of wound healing. Herein, bacterial cellulose (BC) decorated by 4,6-diamino-2-pyrimidinethiol (DAPT)-modified gold nanoparticles (Au-DAPT NPs) is presented as a dressing (BC-Au-DAPT nanocomposites) for treating bacterially infected wounds. BC-Au-DAPT nanocomposites have better efficacy (measured in terms of reduced minimum inhibition concentration) than most of the antibiotics (cefazolin/sulfamethoxazole) against Gram-negative bacteria, while maintaining excellent physicochemical properties including water uptake capability, mechanical strain, and biocompatibility. On Escherichia coli- or Pseudomonas aeruginosa-infected full-thickness skin wounds on rats, the BC-Au-DAPT nanocomposites inhibit bacterial growth and promote wound repair. Thus, the BC-Au-DAPT nanocomposite system is a promising platform for treating superbug-infected wounds., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)