Progress and challenges in bacterial infection theranostics based on functional metal nanoparticles.

The rapid proliferation and infection of bacteria, especially multidrug-resistant bacteria, have become a great threat to global public health. Focusing on the emergence of "super drug-resistant bacteria" caused by the abuse of antibiotics and the insufficient and delayed early diagnosis of bacterial diseases, it is of great research significance to develop new technologies and methods for early targeted detection and treatment of bacterial infection. The exceptional effects of metal nanoparticles based on their unique physical and chemical properties make such systems ideal for the detection and treatment of bacterial infection both in vitro and in vivo. Metal nanoparticles also have admirable clinical application prospects due to their broad antibacterial spectrum, various antibacterial mechanisms and excellent biocompatibility. Herein, we summarized the research progress concerning the mechanism of metal nanoparticles in terms of antibacterial activity together with the detection of bacterial. Representative achievements are selected to illustrate the proof-of-concept in vitro and in vivo applications. Based on these observations, we also give a brief discussion on the current problems and perspective outlook of metal nanoparticles in the diagnosis and treatment of bacterial infection.

Cell Membrane Engineered Polypeptide Nanonets Mimicking Macrophage Aggregates for Enhanced Antibacterial Treatment.

Drug-resistant bacterial infections and their lipopolysaccharide-related inflammatory complications continue to pose significant challenges in traditional treatments. Inspired by the rapid initiation of resident macrophages to form aggregates for efficient antibacterial action, this study proposes a multifunctional and enhanced antibacterial strategy through the construction of novel biomimetic cell membrane polypeptide nanonets (R-DPB-TA-Ce). The design involves the fusion of end-terminal lipidated polypeptides containing side-chain cationic boronic acid groups (DNPLBA) with cell membrane intercalation engineering (R-DPB), followed by coordination with the tannic acid-cerium complex (TA-Ce) to assemble into a biomimetic nanonet through boronic acid-polyphenol-metal ion interactions. In addition to the ability of RAW 264.7 macrophages cell membrane components' (R) ability to neutralize lipopolysaccharide (LPS), R-DPB-TA-Ce demonstrated enhanced capture of bacteria and its LPS, leveraging nanoconfinement-enhanced multiple interactions based on the boronic acid-polyphenol nanonets skeleton combined with polysaccharide. Utilizing these advantages, indocyanine green (ICG) is further employed as a model drug for delivery, showcasing the exceptional treatment effect of R-DPB-TA-Ce as a new biomimetic assembled drug delivery system in antibacterial, anti-inflammatory, and wound healing promotion. Thus, this strategy of mimicking macrophage aggregates is anticipated to be further applicable to various types of cell membrane engineering for enhanced antibacterial treatment.

Neutrophil Extracellular Traps-Inspired Bismuth-Based Polypeptide Nanonets for Synergetic Treatment of Bacterial Infections.

Excessive use of antibiotics and the formation of bacterial biofilms can lead to persistent infections caused by drug-resistant bacteria, rendering ineffective immune responses and even life-threatening. There is an urgent need to explore synergistic antibacterial therapies across all stages of infection. Drawing inspiration from the antibacterial properties of neutrophil extracellular traps (NETs) and integrating the bacterial biofilm dispersal mechanism involving boronic acid-catechol interaction, the multifunctional bismuth-based polypeptide nanonets (PLBA-Bi-Fe-TA) are developed. These nanonets are designed to capture bacteria through a coordination complex involving cationic polypeptides (PLBA) with boronic acid-functionalized side chains, alongside metal ions (bismuth (Bi) and iron (Fe)), and tannic acid (TA). Leveraging the nanoconfinement-enhanced high-contact network-driven multiple efficiency, PLBA-Bi-Fe-TA demonstrates the excellent ability to swiftly capture bacteria and their extracellular polysaccharides. This interaction culminates in the formation of a highly hydrophilic complex, effectively enabling the rapid inhibition and dispersion of antibiotic-resistant bacterial biofilms, while Fe-TA shows mild photothermal ability to further assist fluffy mature biofilm. In addition, Bi is beneficial to regulate the polarization of macrophages to pro-inflammatory phenotype to further kill escaping biofilm bacteria. In summary, this novel approach offers a promising bionic optimization strategy for treating bacterial-associated infections at all stages through synergetic treatment.

Glucose-Responsive ZIF-8 Nanocomposites for Targeted Cancer Therapy through Combining Starvation with Stimulus-Responsive Nitric Oxide Synergistic Treatment.

With the rapid development of nanomedicine, low side effects and high-efficiency green antitumor approaches have attracted great attention. Herein, we report a strategy for the in situ synthesis of graphene oxide@zeolitic imidazolate framework-8 (GOx@ZIF-8) composite nanoparticles with high catalytic efficiency, under mild conditions by adding GOx molecules to the precursor of ZIF-8, and use them as a carrier to achieve efficient loading of l-Arg. In addition. folic-acid-conjugated bovine serum albumin (FA-BSA) has been used to engineer the surface of GOx@ZIF-8-l-Arg composite nanoparticles to enhance their specific recognition of tumor cells. With the high glucose level and low pH in the tumor intracellular environment, FA-BSA/GOx@ZIF-8-l-Arg rapidly consumed the intracellular glucose and produced H2O2, which profusely deteriorated the intracellular environment. Subsequently, a large amount of l-Arg was continuously released from the nanoparticles, reacting with H2O2 to continuously produce a high concentration of nitric oxide (NO), which further damaged the tumor cells. The FA-BSA/GOx@ZIF-8-l-Arg composite nanoparticles were cleverly designed to kill cancer cells efficiently through a starvation-NO synergistic process. This emerging green antitumor method has a promising application prospect in targeted therapy for the efficient clearance of cancers.

Near-Infrared Light-Triggered Nitric Oxide Nanogenerators for NO-Photothermal Synergistic Cancer Therapy.

Cancer is still one of the major health issues faced by human beings today. Various nanomaterials have been designed to treat tumors and have made great progress. Herein, we used amino-functionalized metal organic framework (UiO-66-NH2) as superior templates and successfully synthesized the UiO-66-NH2@Aushell composite nanoparticles (UA) with high loading capacity and excellent photothermal properties through a simple and gentle method. In addition, due to the rich pore structure and excellent biocompatibility of the as-prepared composite nanoparticles, the hydrophobic NO donor BNN6 (N,N'-Di-sec-butyl-N,N'-dinitroso-1, 4-phenylenediamine) molecule was efficiently delivered. Based on the phenomenon where BNN6 molecules can decompose and release NO at high temperature, when UiO-66-NH2@Aushell-BNN6 composite nanoparticles (UA-BNN6) entered tumor cells and were irradiated by NIR, the porous gold nanoshells on the surface of composite nanoparticles induced an increase in temperature through the photothermal conversion process and promoted the decomposition of BNN6 molecules, releasing high concentration of NO, thus efficiently killing HeLa cells through the synergistic effect of NO-photothermal therapy. This effective, precise and safe treatment strategy controlled by NIR laser irradiation represents a promising alternative in the field of cancer treatment.

Self-Assembly Fabrication of Honeycomb-like Magnetic-Fluorescent Fe3O4-QDs Nanocomposites for Bimodal Imaging.

Magnetic-fluorescent nanocomposites have a tremendous potential in biomedicine realms as a revolutionary dual-modality probe tool for more accurate medical detection. However, complicated and inefficient postprocesses pose obstacles to obtaining high-quality magnetic-fluorescent nanocomposites. Thus, the fabrication of magnetic-fluorescent functional nanocomposites via a simple, effective, and ideal method remains a challenge and is still waiting to be tapped. The new synthesis approaches are becoming impending demands and probably enable us to address these above-mentioned problems. In this contribution, we present a novel self-assembly synthesis route for the construction of magnetic-fluorescent bimodal imaging nanocomposites rather than adopting sophisticated postpreparative processes. The Fe3O4 and quatum dots (QDs) nanocomposites were cross-linked fleetly by cerium(III) ion driven coordination bonds in which the cerium(III) ions served as the cross-connecting node and the carboxylate groups acted as bridging ligands. The potential application for dual-modality imaging capability was validated on tumor-bearing mice. This ingenious strategy was extremely efficient and handy for the magnetic-fluorescent Fe3O4-QDs nanocomposite construction. Significantly, our cerium(III) ion driven self-assembly method probably has a wide applicability for nanoparticles and organic molecules containing carboxyl groups but extensive explorations are still necessary.

A novel turn-on fluorescent sensor for the sensitive detection of glutathione via gold nanocluster preparation based on controllable ligand-induced etching.

In this study, we report a facile one-pot chemical etching approach to simply and rapidly prepare gold nanoclusters capped with luminol (Lum-AuNCs) in an alkaline aqueous solution at room temperature. A series of characterization studies have been carried out to explore the morphology, the optical properties and chemical components of Lum-AuNCs. The average diameter of Lum-AuNCs is 1.8 ± 0.3 nm, exhibiting fluorescence near 510 nm upon excitation at 420 nm with a quantum yield of 14.29% and an average fluorescence lifetime of 9.47 ns. On the basis of the ligand-induced etching of glutathione (GSH) to the intermediate (luminol capped gold nanoparticles, abbreviated as Lum-AuNPs), a novel and simple method for the fluorescence determination of GSH has been established. The method displays a good linear response in the range of 0.05-300 µM toward GSH with a limit of detection of 35 nM. This detection strategy with high sensitivity and selectivity facilitates its practical application for the detection of GSH levels in cell extracts. The in vitro cell results illustrate that Lum-AuNCs have good cytocompatibility and can be used to readily differentiate normal cells and tumor cells.

Advances and challenges in metallic nanomaterial synthesis and antibacterial applications.

Multi-drug resistant bacterial infection has become one of the most serious threats to global public health. The preparation and application of new antibacterial materials are of great significance for solving the infection problem of bacteria, especially multi-drug resistant bacteria. The exceptional antibacterial effects of metal nanoparticles based on their unique physical and chemical properties make such systems ideal for application as antibacterial drug carriers or self-modified therapeutic agents both in vitro and in vivo. Metal nanoparticles also have admirable clinical application prospects due to their broad antibacterial spectrum, various antibacterial mechanisms and excellent biocompatibility. Nevertheless, the in vivo structural stability, long-term safety and cytotoxicity of the surface modification of metal nanoparticles have yet to be further explored and improved in subsequent studies. Herein, we summarized the research progress concerning the mechanism of metal nanomaterials in terms of antibacterial activity together with the preparation of metal nanostructures. Based on these observations, we also give a brief discussion on the current problems and future developments of metal nanoparticles for antibacterial applications.