With the increased prevalence of antibiotic-resistant bacteria infections, there is a pressed need for innovative antimicrobial agent. Here, we report a benign ε-polylysine/silver nanoparticle nanocomposite (EPL-g-butyl@AgNPs) with polyvalent and synergistic antibacterial effects. EPL-g-butyl@AgNPs exhibited good stability in aqueous solution and effective antibacterial activity against both Gram-negative (P. aeruginosa) and Gram-positive (S. aureus) bacteria without emergence of bacterial resistance. Importantly, the nanocomposites eradicated the antibiotic-resistant bacteria without toxicity to mammalian cells. Analysis of the antibacterial mechanism confirmed that the nanocomposites adhered to the bacterial surface, irreversibly disrupted the membrane structure of the bacteria, subsequently penetrated cells, and effectively inhibited protein activity, which ultimately led to bacteria apoptosis. Notably, the nanocomposites modulated the relative level of CD3 T cells and CD68 macrophages and effectively promoted infected wound healing in diabetic rats. This work improves our understanding of the antibacterial mechanism of AgNPs-based nanocomposites and offers guidance to activity prediction and rational design of effective antimicrobial nanoparticles.

Antibodies have emerged as a fast‐growing category of biopharmaceuticals that have been widely applied in scientific research, medical diagnosis, and disease treatment. However, many antibodies and other biopharmaceuticals display inferior biophysical properties, such as low stability and a propensity to undergo aggregation. Enhancing the stability of biopharmaceuticals is essential for their wide applications. Here, a facile in vitro protective coating strategy based on metal–organic frameworks (MOFs) is proposed to efficiently protect antibodies against perturbation environments and quickly recover them from the MOFs before usage, which avoids introducing protective additives into the body, which may cause biosafety risks. The protected antibodies exhibit extraordinary thermal, chemical, and mechanical stabilities, and they can survive for long‐term storage (>3 weeks) under severe temperature variation (4 ↔ 50 °C) at a fast ramp rate (25 °C min−1). More importantly, the encapsulated antibodies can be easily released as quickly as 10 s with high efficiency (≈100%) to completely remove the MOFs before use. This study paves a new avenue for the facile preparation and storage of biopharmaceuticals represented by antibodies under ambient or perturbation conditions, which may greatly broaden and promote the applications of both MOFs and biopharmaceuticals.

The chronic infections by pathogenic Pseudomonas aeruginosa (P. aeruginosa) remain to be properly addressed. In particular, for drug‐resistant strains, limited medication is available. An in vivo pneumonia model induced by a clinically isolated aminoglycoside resistant strain of P. aeruginosa is developed. Tobramycin clinically treating P. aeruginosa infections is found to be ineffective to inhibit or eliminate this drug‐resistant strain. Here, a newly developed non‐antibiotics based nanoformulation plus near‐infrared (NIR) photothermal treatment shows a remarkable antibacterial efficacy in treating this drug‐resistant pneumonia. The novel formulation contains 50–100 nm long nanorods decorated with two types of glycomimetic polymers to specifically block bacterial LecA and LecB lectins, respectively, which are essential for bacterial biofilm development. Such a 3D display of heteromultivalent glycomimetics on a large scale is inspired by the natural strengthening mechanism for the carbohydrate–lectin interaction that occurs when bacteria initially infects the host. This novel formulation shows the most efficient bacteria inhabitation and killing against P. aeruginosa infection, through lectin blocking and the near‐infrared‐light‐induced photothermal effect of gold nanorods, respectively. Collectively, the novel biomimetic design combined with the photothermal killing capability is expected to be an alternative treatment strategy against the ever‐threatening drug‐resistant infectious diseases when known antibiotics have failed.

Biofilm is closely related to chronic infections and is difficult to eradicate. Development of effective therapy strategies to control biofilm infection is still challenging. Aiming at biofilm architecture, we designed and prepared near-infrared-activated thermosensitive liposomes with photothermal and antibiotic synergistic therapy capacity to eliminate Pseudomonas aeruginosa biofilm. The liposomes with positive charge and small size aided to enter the biofilm microchannels and locally released antibiotics in infection site. The liposomes could remain stable at 37 °C and release about 80% antibiotics over 45 °C. The biofilm dispersion rate was up to 80%, which was a 7- to 8-fold rise compared to excess antibiotic alone, indicating that the localized antibiotic release and photothermal co-therapy improved the antimicrobial efficiency. In vivo drug-loaded liposomes in treating P. aeruginosa-induced abscess exhibited an outstanding therapeutic effect. Furthermore, photothermal treatment could stimulate the expression of bcl2-associated athanogene 3 to prevent normal tissue from thermal damage. The near-infrared-activated nanoparticle carriers had the tremendous therapeutic potential to dramatically enhance the efficacy of antibiotics through thermos-triggered drug release and photothermal therapy.

Traditional covalent organic frameworks (COFs) are prepared via polymerization based on small molecular monomers. However, the employment of polymers as building blocks to construct COFs has not been reported yet. Herein, we create a new concept of polymer covalent organic frameworks (polyCOFs) formed by linear polymers as structural building blocks, which inherit the merits from both COFs and linear polymers. PolyCOFs represent a new category of porous COF materials that demonstrate good crystallinity and high stability. More importantly, benefiting from the flexibility and processability of a linear polymer, polyCOFs can spontaneously form defect-free, flexible, and freestanding membranes that exhibit excellent mechanical properties and undergo reversible mechanical transformation upon exposure to various organic vapors. For the first time, we demonstrated that polyCOF membranes can be used as artificial muscles to perform various complicated motions (e.g., lifting objects, doing “sit-ups”) triggered by vapors. This study bridges the gap between one-dimensional amorphous linear polymers and crystalline polymer frameworks and paves a new avenue to prepare stimuli-responsive actuators using porous COF materials.

Alzheimer's disease (AD) is a progressive and irreversible brain disorder. Recent studies revealed the pivotal role of β-amyloid (Aβ) in AD. However, there is no conclusive indication that the existing therapeutic strategies exerted any effect on the mitigation of Aβ-induced neurotoxicity and the elimination of Aβ aggregates simultaneously in vivo. Herein, we developed a novel nanocomposite that can eliminate toxic Aβ aggregates and mitigate Aβ-induced neurotoxicity in AD mice. This nanocomposite was designed to be a small-sized particle (14 ± 4 nm) with Aβ-binding peptides (KLVFF) integrated on the surface. The nanocomposite was prepared by wrapping a protein molecule with a cross-linked KLVFF-containing polymer layer synthesized by in situ polymerization. The presence of the nanocomposite remarkably changed the morphology of Aβ aggregates, which led to the formation of Aβ/ nanocomposite coassembled nanoclusters instead of Aβ oligomers. With the reduction of the pathological Aβ oligomers, the nanocomposites attenuated the Aβ-induced neuron damages, regained endocranial microglia's capability to phagocytose Aβ, and eventually protected hippocampal neurons against apoptosis. Thus, we anticipate that the small-sized nanocomposite will potentially offer a feasible strategy in the development of novel AD treatments.

The clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR‐associated (Cas) enzyme, Cas13a, holds great promise in cancer treatment due to its potential for selective destruction of tumor cells via collateral effects after target recognition. However, these collateral effects do not specifically target tumor cells and may cause safety issues when administered systemically. Herein, a dual‐locking nanoparticle (DLNP) that can restrict CRISPR/Cas13a activation to tumor tissues is described. DLNP has a core–shell structure, in which the CRISPR/Cas13a system (plasmid DNA, pDNA) is encapsulated inside the core with a dual‐responsive polymer layer. This polymer layer endows the DLNP with enhanced stability during blood circulation or in normal tissues and facilitates cellular internalization of the CRISPR/Cas13a system and activation of gene editing upon entry into tumor tissue. After carefully screening and optimizing the CRISPR RNA (crRNA) sequence that targets programmed death‐ligand 1 (PD‐L1), DLNP demonstrates the effective activation of T‐cell‐mediated antitumor immunity and the reshaping of immunosuppressive tumor microenvironment (TME) in B16F10‐bearing mice, resulting in significantly enhanced antitumor effect and improved survival rate. Further development by replacing the specific crRNA of target genes can potentially make DLNP a universal platform for the rapid development of safe and efficient cancer immunotherapies.

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