Devastating the Supply Wagons: Multifaceted Liposomes Capable of Exhausting Tumor to Death via Triple Energy Depletion.

The anabolism of tumor cells can not only support their proliferation, but also endow them with a steady influx of exogenous nutrients. Therefore, consuming metabolic substrates or limiting access to energy supply can be an effective strategy to impede tumor growth. Herein, a novel treatment paradigm of starving-like therapy-triple energy-depleting therapy-is illustrated by glucose oxidase (GOx)/dc-IR825/sorafenib liposomes (termed GISLs), and such a triple energy-depleting therapy exhibits a more effective tumor-killing effect than conventional starvation therapy that only cuts off one of the energy supplies. Specifically, GOx can continuously consume glucose and generate toxic H2O2 in the tumor microenvironment (including tumor cells). After endocytosis, dc-IR825 (a near-infrared cyanine dye) can precisely target mitochondria and exert photodynamic and photothermal activities upon laser irradiation to destroy mitochondria. The anti-angiogenesis effect of sorafenib can further block energy and nutrition supply from blood. This work exemplifies a facile and safe method to exhaust the energy in a tumor from three aspects and starve the tumor to death and also highlights the importance of energy depletion in tumor treatment. It is hoped that this work will inspire the development of more advanced platforms that can combine multiple energy depletion therapies to realize more effective tumor treatment.

See the Unseen: Red-Emissive Carbon Dots for Visualizing the Nucleolar Structures in Two Model Animals and In Vivo Drug Toxicity.

Nucleolus, which participates in many crucial cellular activities, is an ideal target for evaluating the state of a cell or an organism. Here, bright red-emissive carbon dots (termed CPCDs) with excitation-independent/polarity-dependent fluorescence emission are synthesized by a one-step hydrothermal reaction between congo red and p-phenylenediamine. The CPCDs can achieve wash-free, real-time, long-term, and high-quality nucleolus imaging in live cells, as well as in vivo imaging of two common model animals-zebrafish and Caenorhabditis elegans (C. elegans). Strikingly, CPCDs realize the nucleolus imaging of organs/flowing blood cells in zebrafish at a cellular level for the first time, and the superb nucleolus imaging of C. elegans suggests that the germ cells in the spermatheca probably have no intact nuclei. These previously unachieved imaging results of the cells/tissues/organs may guide the zebrafish-related studies and benefit the research of C. elegans development. More importantly, a novel strategy based on CPCDs for in vivo toxicity evaluation of materials/drugs (e.g., Ag+ ), which can visualize the otherwise unseen injuries in zebrafish, is developed. In conclusion, the CPCDs represent a robust tool for visualizing the structures and dynamic behaviors of live zebrafish and C. elegans, and may find important applications in cell biology and toxicology.

Platinum-Coordinated Dual-Responsive Nanogels for Universal Drug Delivery and Combination Cancer Therapy.

Developing a universal nanoplatform for efficient delivery of various drugs to target sites is urgent for overcoming various biological barriers and realizing combinational cancer treatment. Nanogels, with the advantages of both hydrogels and nanoparticles, may hold potential for addressing the above issue. Here, a dual-responsive nanogel platform (HPC nanogel) is constructed using ß-cyclodextrin-conjugated hyaluronic acid (HA-ßCD), polyethyleneimine (PEI), and cisplatin. HA-ßCD and PEI compose the skeleton of the nanogel, and cisplatin molecules provide the junctions inside the skeleton, thus affording a multiple interactions-based nanogel. Besides, HA endows the nanogel with hyaluronidase (HAase)-responsiveness, and cisplatin guarantees the glutathione (GSH)-responsive ability, which make the nanogel a dual-responsive platform that can degrade and release the loaded drugs when encountering HAase or GSH. Additionally, the HPC nanogel possesses excellent small-molecule drug and protein loading and intracellular delivery capabilities. Especially, for proteins, their intracellular delivery via nanogels is not hindered by serum proteins, and the enzymes delivered into cells still maintain their catalytic activities. Furthermore, the nanogel can codeliver different cargoes to achieve "cocktail" chemotherapeutic efficacy and realize combination cancer therapy. Overall, the HPC nanogel can serve as a multifunctional platform capable of delivering desired drugs to treat cancer or other diseases.

Cell surface-localized imaging and sensing.

Systematically dissecting the molecular basis of the cell surface as well as its related biological activities is considered as one of the most cutting-edge fields in fundamental sciences. The advent of various advanced cell imaging techniques allows us to gain a glimpse of how the cell surface is structured and coordinated with other cellular components to respond to intracellular signals and environmental stimuli. Nowadays, cell surface-related studies have entered a new era featured by a redirected aim of not just understanding but artificially manipulating/remodeling the cell surface properties. To meet this goal, biologists and chemists are intensely engaged in developing more maneuverable cell surface labeling strategies by exploiting the cell's intrinsic biosynthetic machinery or direct chemical/physical binding methods for imaging, sensing, and biomedical applications. In this review, we summarize the recent advances that focus on the visualization of various cell surface structures/dynamics and accurate monitoring of the microenvironment of the cell surface. Future challenges and opportunities in these fields are discussed, and the importance of cell surface-based studies is highlighted.

Repurposing Erythrocytes as a "Photoactivatable Bomb": A General Strategy for Site-Specific Drug Release in Blood Vessels.

Tumor vasculature has long been considered as an extremely valuable therapeutic target for cancer therapy, but how to realize controlled and site-specific drug release in tumor blood vessels remains a huge challenge. Despite the widespread use of nanomaterials in constructing drug delivery systems, they are suboptimal in principle for meeting this demand due to their easy blood cell adsorption/internalization and short lifetime in the systemic circulation. Here, natural red blood cells (RBCs) are repurposed as a remote-controllable drug vehicle, which retains RBC's morphology and vessel-specific biodistribution pattern, by installing photoactivatable molecular triggers on the RBC membrane via covalent conjugation with a finely tuned modification density. The molecular triggers can burst the RBC vehicle under short and mild laser irradiation, leading to a complete and site-specific release of its payloads. This cell-based vehicle is generalized by loading different therapeutic agents including macromolecular thrombin, a blood clotting-inducing enzyme, and a small-molecule hypoxia-activatable chemodrug, tirapazamine. In vivo results demonstrate that the repurposed "anticancer RBCs" exhibit long-term stability in systemic circulation but, when tumors receive laser irradiation, precisely releases their cargoes in tumor vessels for thrombosis-induced starvation therapy and local deoxygenation-enhanced chemotherapy. This study proposes a general strategy for blood vessel-specific drug delivery.

A Highly Selective Turn-on Fluorescent and Naked-eye Colourimetric Dual-channel Probe for Cyanide Anions Detection in Water Samples.

A highly selective turn-on fluorescent and naked-eye colourimetric dual-channel probe for cyanide anions (CN-) has been designed and characterized. In the mixed solution (DMSO / H2O, 9:1, v / v), only CN- could cause an increase in the UV absorption intensity and the corresponding fluorescence intensity increased, and other anions had no significant effect on the probe. After treatment with cyanide in the probe solution, the solution showed a noticeable colour change, from light yellow to purple. Moreover, a fluorescence spectrophotometer can be used to observe that the fluorescence intensity of the solution is significantly enhanced. The response of the colourimetric and fluorescent dual-channel probe to CN- was attributed to nucleophilic addition, and the mechanism was determined by 1H NMR spectroscopy. In addition, this probe was used to detect CN- in actual water samples, including river water, drinking water, and tap water. The spiked CN- recovery rate is very high (97.2%-100.06%), and analytical precision is also very high (RSD < 2%), which shows its feasibility and reliability for detecting cyanide ions in actual water samples.

A Glucose/Oxygen-Exhausting Nanoreactor for Starvation- and Hypoxia-Activated Sustainable and Cascade Chemo-Chemodynamic Therapy.

Fenton reaction-mediated chemodynamic therapy (CDT) can kill cancer cells via the conversion of H2 O2 to highly toxic HO•. However, problems such as insufficient H2 O2 levels in the tumor tissue and low Fenton reaction efficiency severely limit the performance of CDT. Here, the prodrug tirapazamine (TPZ)-loaded human serum albumin (HSA)-glucose oxidase (GOx) mixture is prepared and modified with a metal-polyphenol network composed of ferric ions (Fe3+ ) and tannic acid (TA), to obtain a self-amplified nanoreactor termed HSA-GOx-TPZ-Fe3+ -TA (HGTFT) for sustainable and cascade cancer therapy with exogenous H2 O2 production and TA-accelerated Fe3+ /Fe2+ conversion. The HGTFT nanoreactor can efficiently convert oxygen into HO• for CDT, consume glucose for starvation therapy, and provide a hypoxic environment for TPZ radical-mediated chemotherapy. Besides, it is revealed that the nanoreactor can significantly elevate the intracellular reactive oxygen species content and hypoxia level, decrease the intracellular glutathione content, and release metal ions in the tumors for metal ion interference therapy (also termed "ion-interference therapy" or "metal ion therapy"). Further, the nanoreactor can also increase the tumor's hypoxia level and efficiently inhibit tumor growth. It is believed that this tumor microenvironment-regulable nanoreactor with sustainable and cascade anticancer performance and excellent biosafety represents an advance in nanomedicine.

Palladium Nanosheets as Safe Radiosensitizers for Radiotherapy.

Many noble metal-based nanoparticles have emerged for applications in cancer radiotherapy in recent years, but few investigations have been carried out for palladium nanoparticles. Herein, palladium nanosheets (Pd NSs), which possess a sheetlike morphology with a diameter of ∼14 nm and a thickness of ∼2 nm, were utilized as a sensitizer to improve the performance of radiotherapy. It was found that Pd NSs alone did not decrease the cell viability after treatment for as long as 130 h, suggesting the excellent cytocompatibility of the nanoagents. However, the viability of cancer cells treated with X-ray irradiation became lower, and the viability became even lower if the cells were co-treated with X-ray and Pd NSs, indicating the radiosensitization effect of Pd NSs. Additionally, compared with X-ray irradiation, the combined treatment of Pd NSs and X-ray irradiation induced the generation of more DNA double-stranded breaks and reactive oxygen species within cancer cells, which eventually caused elevated cell apoptosis. Moreover, in vivo experiments also verified the radiosensitization effect and the favorable biocompatibility of Pd NSs, indicating their potential for acquiring satisfactory in vivo radiotherapeutic effect at lower X-ray doses. It is believed that the present research will open new avenues for the application of noble metal-based nanoparticles in radiosensitization.

Molecular Targeting-Mediated Mild-Temperature Photothermal Therapy with a Smart Albumin-Based Nanodrug.

Photothermal therapy (PTT) usually requires hyperthermia >50 °C for effective tumor ablation, which inevitably induces heating damage to the surrounding normal tissues/organs. Moreover, low tumor retention and high liver accumulation are the two main obstacles that significantly limit the efficacy and safety of many nanomedicines. To solve these problems, a smart albumin-based tumor microenvironment-responsive nanoagent is designed via the self-assembly of human serum albumin (HSA), dc-IR825 (a cyanine dye and a photothermal agent), and gambogic acid (GA, a heat shock protein 90 (HSP90) inhibitor and an anticancer agent) to realize molecular targeting-mediated mild-temperature PTT. The formed HSA/dc-IR825/GA nanoparticles (NPs) can escape from mitochondria to the cytosol through mitochondrial disruption under near-infrared (NIR) laser irradiation. Moreover, the GA molecules block the hyperthermia-induced overexpression of HSP90, achieving the reduced thermoresistance of tumor cells and effective PTT at a mild temperature (<45 °C). Furthermore, HSA/dc-IR825/GA NPs show pH-responsive charge reversal, effective tumor accumulation, and negligible liver deposition, ultimately facilitating synergistic mild-temperature PTT and chemotherapy. Taken together, the NIR-activated NPs allow the release of molecular drugs more precisely, ablate tumors more effectively, and inhibit cancer metastasis more persistently, which will advance the development of novel mild-temperature PTT-based combination strategies.

Water-Dispersible Candle Soot-Derived Carbon Nano-Onion Clusters for Imaging-Guided Photothermal Cancer Therapy.

Herein, water-dispersible carbon nano-onion clusters (CNOCs) with an average hydrodynamic size of ≈90 nm are prepared by simply sonicating candle soot in a mixture of oxidizing acid. The obtained CNOCs have high photothermal conversion efficiency (57.5%), excellent aqueous dispersibility (stable in water for more than a year without precipitation), and benign biocompatibility. After polyethylenimine (PEI) and poly(ethylene glycol) (PEG) modification, the resultant CNOCs-PEI-PEG have a high photothermal conversion efficiency (56.5%), and can realize after-wash photothermal cancer cell ablation due to their ultrahigh cellular uptake (21.3 pg/cell), which is highly beneficial for the selective ablation of cancer cells via light-triggered intracellular heat generation. More interestingly, the cellular uptake of CNOCs-PEI-PEG is so high that the internalized nanoagents can be directly observed under a microscope without fluorescent labeling. Besides, in vivo experiments reveal that CNOCs-PEI-PEG can be used for photothermal/photoacoustic dual-modal imaging-guided photothermal therapy after intravenous administration. Furthermore, CNOCs-PEI-PEG can be efficiently cleared from the mouse body within a week, ensuring their excellent long-term biosafety. To the best of the authors' knowledge, the first example of using candle soot as raw material to prepare water-dispersible onion-like carbon nanomaterials for cancer theranostics is represented herein.

Role of Cholesterol Conjugation in the Antibacterial Photodynamic Therapy of Branched Polyethylenimine-Containing Nanoagents.

Photodynamic therapy is a promising approach for fighting bacterial infections because it can induce few side effects, develop no drug resistance, and realize precise treatment. However, most photosensitizers (PSs) have the disadvantages of poor water-solubility, severe self-quenching, and potential toxicity. Here, the cationic polymer polyethyleneimine (PEI) was used to prepare a cholesterol- and chlorin e6 (Ce6, a common PS)-conjugated compound via the carboxyl-amine reaction or the acyl chloride-amine reaction (abbreviated as Chol-PEI-Ce6). The as-prepared Chol-PEI-Ce6 molecules can self-assemble into close-to-spherical nanoparticles (NPs) with an average diameter of ∼15 nm and can bind to the bacterial surfaces via the synergistic hydrophobic insertion of the cholesterol moieties and electrostatic interaction between the cationic amine groups of PEI and the bacterial surfaces. Upon light irradiation, the NPs can effectively inactivate both Gram-positive and Gram-negative bacteria. Besides, the interaction between Chol-PEI-Ce6 NPs and bacteria markedly enhances the production of intracellular reactive oxygen species after light irradiation, which may account for the excellent antibacterial performance of the NPs. More importantly, the NPs possess negligible dark cytotoxicity and good hemocompatibility. Therefore, the present work may have strong implications for developing novel antibacterial agents to fight against bacterial infections.

Glycol Chitosan: A Water-Soluble Polymer for Cell Imaging and Drug Delivery.

Glycol chitosan (GC), a water-soluble chitosan derivative with hydrophilic ethylene glycol branches, has both hydrophobic segments for the encapsulation of various drugs and reactive functional groups for facile chemical modifications. Over the past two decades, a variety of molecules have been physically encapsulated within or chemically conjugated with GC and its derivatives to construct a wide range of functional biomaterials. This review summarizes the recent advances of GC-based materials in cell surface labeling, multimodal tumor imaging, and encapsulation and delivery of drugs (including chemotherapeutics, photosensitizers, nucleic acids, and antimicrobial agents) for combating cancers and microbial infections. Besides, different strategies for GC modifications are also highlighted with the aim to shed light on how to endow GC and its derivatives with desirable properties for therapeutic purposes. In addition, we discuss both the promises and challenges of the GC-derived biomaterials.

Development of a Light-Controlled Nanoplatform for Direct Nuclear Delivery of Molecular and Nanoscale Materials.

Research on nanomedicines has rapidly progressed in the past few years. However, due to the limited size of nuclear pores (9-12 nm), the nuclear membrane remains a difficult barrier to many nucleus-targeting agents. Here, we report the development of a general platform to effectively deliver chemical compounds such as drug molecules or nanomaterials into cell nuclei. This platform consists of a polyamine-containing polyhedral oligomeric silsesquioxane (POSS) unit, a hydrophilic polyethylene glycol (PEG) chain, and the photosensitizer rose bengal (RB), which can self-assemble into nanoparticles (denoted as PPR NPs). Confocal fluorescence imaging showed that PPR NPs mainly located in lysosomes after cellular internalization. After mild light irradiation, however, PPR NPs effectively disrupted lysosomal structures by singlet oxygen (1O2) oxidation and substantially accumulated on nuclear membranes, which enabled further disruption of the membrane integrity and promoted their final nuclear entry. Next, we selected two chemotherapeutic agents (10-hydroxycamptothecine and docetaxel) and a fluorescent dye (DiD) as payloads of PPR NPs and successfully demonstrated that this nanocarrier could efficiently deliver them into cell nuclei in a light-controlled manner. In addition to molecular compounds, we have also demonstrated that PPR NPs could facilitate the nuclear entry of nanomaterials, including Prussian blue NPs as well as gold nanorods. Compared to traditional strategies for nuclear delivery, this highly controllable nanoplatform avoids complicated modification of nucleus-targeting ligands and is generally applicable to both molecular compounds and nanomaterials.

Long-Time Plasma Membrane Imaging Based on a Two-Step Synergistic Cell Surface Modification Strategy.

Long-time stable plasma membrane imaging is difficult due to the fast cellular internalization of fluorescent dyes and the quick detachment of the dyes from the membrane. In this study, we developed a two-step synergistic cell surface modification and labeling strategy to realize long-time plasma membrane imaging. Initially, a multisite plasma membrane anchoring reagent, glycol chitosan-10% PEG2000 cholesterol-10% biotin (abbreviated as "GC-Chol-Biotin"), was incubated with cells to modify the plasma membranes with biotin groups with the assistance of the membrane anchoring ability of cholesterol moieties. Fluorescein isothiocyanate (FITC)-conjugated avidin was then introduced to achieve the fluorescence-labeled plasma membranes based on the supramolecular recognition between biotin and avidin. This strategy achieved stable plasma membrane imaging for up to 8 h without substantial internalization of the dyes, and avoided the quick fluorescence loss caused by the detachment of dyes from plasma membranes. We have also demonstrated that the imaging performance of our staining strategy far surpassed that of current commercial plasma membrane imaging reagents such as DiD and CellMask. Furthermore, the photodynamic damage of plasma membranes caused by a photosensitizer, Chlorin e6 (Ce6), was tracked in real time for 5 h during continuous laser irradiation. Plasma membrane behaviors including cell shrinkage, membrane blebbing, and plasma membrane vesiculation could be dynamically recorded. Therefore, the imaging strategy developed in this work may provide a novel platform to investigate plasma membrane behaviors over a relatively long time period.

Multivalent Aptamer-Based Lysosome-Targeting Chimeras (LYTACs) Platform for Mono- or Dual-Targeted Proteins Degradation on Cell Surface.

Selective protein degradation platforms have opened novel avenues in therapeutic development and biological inquiry. Antibody-based lysosome-targeting chimeras (LYTACs) have emerged as a promising technology that extends the scope of targeted protein degradation to extracellular targets. Aptamers offer an advantageous alternative owing to their potential for modification and manipulation toward a multivalent state. In this study, a chemically engineered platform of multivalent aptamer-based LYTACs (AptLYTACs) is established for the targeted degradation of either single or dual protein targets. Leveraging the biotin-streptavidin system as a molecular scaffold, this investigation reveals that trivalently mono-targeted AptLYTACs demonstrate optimum efficiency in degrading membrane proteins. The development of this multivalent AptLYTACs platform provides a principle of concept for mono-/dual-targets degradation, expanding the possibilities of targeted protein degradation.

A red blood cell-derived bionic microrobot capable of hierarchically adapting to five critical stages in systemic drug delivery.

The tumour-targeting efficiency of systemically delivered chemodrugs largely dictates the therapeutic outcome of anticancer treatment. Major challenges lie in the complexity of diverse biological barriers that drug delivery systems must hierarchically overcome to reach their cellular/subcellular targets. Herein, an "all-in-one" red blood cell (RBC)-derived microrobot that can hierarchically adapt to five critical stages during systemic drug delivery, that is, circulation, accumulation, release, extravasation, and penetration, is developed. The microrobots behave like natural RBCs in blood circulation, due to their almost identical surface properties, but can be magnetically manipulated to accumulate at regions of interest such as tumours. Next, the microrobots are "immolated" under laser irradiation to release their therapeutic cargoes and, by generating heat, to enhance drug extravasation through vascular barriers. As a coloaded agent, pirfenidone (PFD) can inhibit the formation of extracellular matrix and increase the penetration depth of chemodrugs in the solid tumour. It is demonstrated that this system effectively suppresses both primary and metastatic tumours in mouse models without evident side effects, and may represent a new class of intelligent biomimicking robots for biomedical applications.

A ferroptosis-reinforced nanocatalyst enhances chemodynamic therapy through dual H2O2 production and oxidative stress amplification.

The existence of a delicate redox balance in tumors usually leads to cancer treatment failure. Breaking redox homeostasis by amplifying oxidative stress and reducing glutathione (GSH) can accelerate cancer cell death. Herein, we construct a ferroptosis-reinforced nanocatalyst (denoted as HBGL) to amplify intracellular oxidative stress via dual H2O2 production-assisted chemodynamic therapy (CDT). Specifically, a long-circulating liposome is employed to deliver hemin (a natural iron-containing substrate for Fenton reaction and ferroptosis), ß-lapachone (a DNA topoisomerase inhibitor with H2O2 generation capacity for chemotherapy), and glucose oxidase (which can consume glucose for starvation therapy and generate H2O2). HBGL can achieve rapid, continuous, and massive H2O2 and •OH production and GSH depletion in cancer cells, resulting in increased intracellular oxidative stress. Additionally, hemin can reinforce the ferroptosis-inducing ability of HBGL, which is reflected in the downregulation of glutathione peroxidase-4 and the accumulation of lipid peroxide. Notably, HBGL can disrupt endo/lysosomes and impair mitochondrial function in cancer cells. HBGL exhibits effective tumor-killing ability without eliciting obvious side effects, indicating its clinical translation potential for synergistic starvation therapy, chemotherapy, ferroptosis therapy, and CDT. Overall, this nanocatalytic liposome may be a promising candidate for achieving potentiated cancer treatment.

Abscisic acid mediated strawberry receptacle ripening involves the interplay of multiple phytohormone signaling networks.

As a canonical non-climacteric fruit, strawberry (Fragaria spp.) ripening is mainly mediated by abscisic acid (ABA), which involves multiple other phytohormone signalings. Many details of these complex associations are not well understood. We present an coexpression network, involving ABA and other phytohormone signalings, based on weighted gene coexpression network analysis of spatiotemporally resolved transcriptome data and phenotypic changes of strawberry receptacles during development and following various treatments. This coexpression network consists of 18,998 transcripts and includes transcripts related to phytohormone signaling pathways, MADS and NAC family transcription factors and biosynthetic pathways associated with fruit quality. Members of eight phytohormone signaling pathways are predicted to participate in ripening and fruit quality attributes mediated by ABA, of which 43 transcripts were screened to consist of the hub phytohormone signalings. In addition to using several genes reported from previous studies to verify the reliability and accuracy of this network, we explored the role of two hub signalings, small auxin up-regulated RNA 1 and 2 in receptacle ripening mediated by ABA, which are also predicted to contribute to fruit quality. These results and publicly accessible datasets provide a valuable resource to elucidate ripening and quality formation mediated by ABA and involves multiple other phytohormone signalings in strawberry receptacle and serve as a model for other non-climacteric fruits.

Fluorescent dendrimer-based probes for cell membrane imaging: Zebrafish epidermal labeling-based toxicity evaluation.

Visualizing the plasma membrane of living mammalian cells both in vitro and in vivo is crucial for tracking their cellular activities. However, due to the complex and dynamic nature of the plasma membrane, most commercial dyes for membrane staining can only realize very limited imaging performance. Thus, precise and stable plasma membrane imaging remains technically challenging. Here, by taking advantage of the small, well-defined, and amine-rich dendrimers, we prepared poly(ethylene glycol)-cholesterol (PEG-Chol)-conjugated and cyanine dye (e.g., cyanine2, cyanine3, and cyanine5)-labeled dendrimer nanoprobes (termed DPC-Cy2, DPC-Cy3, and DPC-Cy5 NPs). It was revealed that these probes enabled universal, wash-free, long-term (at least 8 h), and multicolor (green, yellow, and red) plasma membrane labeling of a variety of live mammalian cells. Further, we confirmed that the nanoprobes (using DPC-Cy5 as a representative) could achieve high-quality, wash-free, and stable cell surface labeling of live zebrafish embryos. More importantly, we demonstrated that our probes could act as biosensors to visualize the toxicity of metal-organic frameworks (MOFs) toward the epidermal cells of zebrafish embryos, and thus they hold great potential for identifying the toxic effect of drugs/materials at the single-cell scale or in live animals. The present work highlights the advantages of utilizing dendrimers for constructing functional imaging materials, and it is also believed that the fluorescent dendrimer nanoprobes developed in this work may find wide applications like cell imaging, drug toxicity evaluation, and cellular state monitoring.

Direct chemical editing of Gram-positive bacterial cell walls via an enzyme-catalyzed oxidative coupling reaction.

Chemically manipulating bacterial surface structures, a cutting-edge research direction in the biomedical field, predominantly relies on metabolic labeling by now. However, this method may involve daunting precursor synthesis and only labels nascent surface structures. Here, we report a facile and rapid modification strategy based on a tyrosinase-catalyzed oxidative coupling reaction (TyOCR) for bacterial surface engineering. This strategy employs phenol-tagged small molecules and tyrosinase to initiate direct chemical modification of Gram-positive bacterial cell walls with high labeling efficiency, while Gram-negative bacteria are inert to this modification due to the hindrance of an outer membrane. By using the biotin‒avidin system, we further present the selective deposition of various materials, including photosensitizer, magnetic nanoparticle, and horseradish peroxidase, on Gram-positive bacterial surfaces, and realize the purification/isolation/enrichment and naked-eye detection of bacterial strains. This work demonstrates that TyOCR is a promising strategy for engineering live bacterial cells.