Ultrasensitive Electrochemiluminescence Immunosensor for Bladder Marker Human Complement Factor H-Related Protein Detection.

The development of noninvasive and sensitive detection methods for the early diagnosis and monitoring of bladder cancer is critical but challenging. Herein, an ultrasensitive electrochemiluminescence (ECL) immunosensor that uses Ru(bpy)32+-metal-organic framework (Ru-MOF) nanospheres and a DNA tetrahedral (TDN) probe was established for bladder cancer marker complement factor H-related protein (CFHR1) detection. The synthesized Ru(bpy)32+-metal-organic frameworks (Ru-MOFs) served as a linked substrate for immobilization of AuNPs and antibody (Ab2) to prepare the ECL signal probe (Ru-MOF@AuNPs-Ab2), exhibiting a stable and strengthened ECL emission. At the same time, the inherent advantages of TDN probes on the electrode as the capture probe (TDN-Ab1) improve the accessibility of targets to probes. In the presence of CFHR1, the signal probe Ru-MOF@AuNPs-Ab2 was modified on the electrode through immune binding, thereby obtaining an outstanding ECL signal. As expected, the developed ECL immunosensor exhibited splendid performance for CFHR1 detection in the range of 0.1 fg/mL to 10 pg/mL with a quite low detection limit of 0.069 fg/mL. By using the proposed strategy to detect CFHR1 from urine, it showed acceptable accuracy, which can effectively distinguish between bladder cancer patients and healthy samples. This work contributes to a novel, noninvasive, and accurate method for early clinical diagnosis of bladder cancer.

The recent advance of precisely designed membranes for sieving.

Developing new membranes with both high selectivity and permeability is critical in membrane science since conventional membranes are often limited by the trade-off between selectivity and permeability. In recent years, the emergence of advanced materials with accurate structures at atomic or molecular scale, such as metal organic framework, covalent organic framework, graphene, has accelerated the development of membranes, which benefits the precision of membrane structures. In this review, current state-of-the-art membranes are first reviewed and classified into three different types according to the structures of their building blocks, including laminar structured membranes, framework structured membranes and channel structured membranes, followed by the performance and applications for representative separations (liquid separation and gas separation) of these precisely designed membranes. Last, the challenges and opportunities of these advanced membranes are also discussed.

Interactions of Nanomaterials with Gut Microbiota and Their Applications in Cancer Therapy.

Cancer treatment is a challenge by its incredible complexity. As a key driver and player of cancer, gut microbiota influences the efficacy of cancer treatment. Modalities to manipulate gut microbiota have been reported to enhance antitumor efficacy in some cases. Nanomaterials (NMs) have been comprehensively applied in cancer diagnosis, imaging, and theranostics due to their unique and excellent properties, and their effectiveness is also influenced by gut microbiota. Nanotechnology is capable of targeting and manipulating gut microbiota, which offers massive opportunities to potentiate cancer treatment. Given the complexity of gut microbiota-host interactions, understanding NMs-gut interactions and NMs-gut microbiota interactions are important for applying nanotechnologies towards manipulating gut microbiota in cancer prevention and treatment. In this review, we provide an overview of NMs-gut interactions and NMs-gut microbiota interactions and highlight the influences of gut microbiota on the diagnosis and treatment effects of NMs, further illustrating the potential of nanotechnologies in cancer therapy. Investigation of the influences of NMs on cancer from the perspective of gut microbiota will boost the prospect of nanotechnology intervention of gut microbiota for cancer therapy.

Biomimetic 3D Recognition with 2D Flexible Nanoarchitectures for Ultrasensitive and Visual Extracellular Vesicle Detection.

Despite increasing recognition of extracellular vesicles being important circulating biomarkers in disease diagnosis and prognosis, current strategies for extracellular vesicle detection remain limited due to the compromised sample purification and extensive labeling procedures in complex body fluids. Here, we developed a 2D magnetic platform that greatly improves capture efficiency and readily realizes visible signal conversion for extracellular vesicle detection. The technology, termed high-affinity recognition and visual extracellular vesicle testing (HARVEST), leverages 2D flexible Fe3O4-MoS2 nanostructures to recognize extracellular vesicles through multidentate affinity binding and feasible magnetic separation, thus enhancing the extracellular vesicle capture performance with both yield and separation time, affording high sensitivity with the detection limit of 20 extracellular vesicle particles/µL. Through integration with lipid labeling chemistry and the fluorescence visualization system, the platform enables rapid and visible detection. The number of extracellular vesicles can be feasibly determined by smart mobile phones, readily adapted for point-of-care diagnosis. When clinically evaluated, the strategy accurately differentiates melanoma samples from the normal cohort with an AUC of 0.98, demonstrating the efficient extracellular vesicle detection strategy with 2D flexible platforms for cancer diagnosis.

Intracellular miRNA-Triggered Surface-Enhanced Raman Scattering Imaging and Dual Gene-Silencing Therapy of Cancer Cell.

Development of theranostic nanosystems integrating cascaded surface-enhanced Raman scattering (SERS) imaging and gene silencing therapy for accurate cancer diagnosis and treatment is still a big challenge and rarely reported. Herein, a novel Au nanoparticles (AuNPs)-based theranostic nanosystem containing AuNP-Ys and AuNP-Ds for highly sensitive and specific cancer diagnosis and treatment was proposed for cascaded SERS imaging of intracellular cancer-related miR-106a and miR-106a-triggered DNAzyme-based dual gene-silencing therapy of cancer cells. The AuNP-Ys were prepared by modifying the AuNPs with specially designed Y-motifs, and the AuNP-Ds were obtained by colabeling Raman molecules and dsDNA linkers on AuNPs. When identifying the intracellular cancer-related miRNAs, the Y-motifs and dsDNA linkers undergoes miRNA-triggered ATP-driven conformational transitions and releases the miRNA for recycling, which results in the formation of AuNP network nanostructures to generate significantly enhanced SERS signals for sensitive identification of the cancer cells as well as the amplification and specific activation of DNAzymes to catalyze the Mg2+-assisted cleavage of the Survivin and c-Jun mRNAs for effective dual gene-silencing therapy of cancer cells. The AuNP-based theranostic nanosystem achieves the synergism of target-triggered SERS imaging and DNAzyme-based dual gene-silencing therapy with enhanced specificity, sensitivity, and curative effect, which can be a powerful tool for accurate diagnosis and efficient treatment of cancers.

Dysbiosis of gut microbiota and intestinal damage in mice induced by a single intravenous exposure to CdTe quantum dots at low concentration.

Although quantum dots (QDs) have shown great potential for various biomedical applications, their potential toxicity still needs to be comprehensively investigated. Previous studies showed that intravenous exposure of CdTe QDs at low concentration did not lead to obvious in vivo toxicity in the long term. However, the influence of CdTe QDs on the gut microbiota and the intestine is still unknown. Here, we explored whether single intravenous injection of CdTe QDs at low concentration can affect the gut microbiota and intestine of mice in short term. The results showed that CdTe QDs caused an imbalance of gut microbiota, especially the rapid increase in Lactobacillus on day 1 post-treatment. Meanwhile, the intestine exhibited the promotion of oxidative stress, inflammatory response, and hemorrhaging on days 5 and 15. These results demonstrate that the gut microbiota and the intestine are very sensitive to the toxicity of low-concentration CdTe QDs. This study provides further insight and method for the biosafety evaluation of nanomaterials.

Cu2 MoS4 Nanozyme with NIR-II Light Enhanced Catalytic Activity for Efficient Eradication of Multidrug-Resistant Bacteria.

Nanozymes with unique enzyme-like catalytic properties and versatile functionalities are particularly attractive for the treatment of bacterial infections, especially for combating drug-resistant bacteria. However, inherently low catalytic activity significantly limits their antibacterial performance. Herein, a new near-infrared II (NIR-II) light responsive nanozyme (Cu2 MoS4 nanoplates, CMS NPs) is developed for efficient eradication of multidrug-resistant (MDR) bacteria. CMS NPs with intrinsic dual enzyme-like property can generate reactive oxygen species (ROS) by catalysis. Importantly, CMS NPs show NIR-II light enhanced oxidase- and peroxidase-like catalytic activities to improve ROS generation for highly efficient killing of bacteria. In vitro results demonstrate that CMS NPs (40 µg mL-1 ) achieve rapid killing of 8 log MDR Escherichia coli and 6 log MDR Staphylococcus aureus (S. aureus) under NIR-II light irradiation (1064 nm, 1 W cm-2 ) in 10 min. Moreover, CMS NPs exhibit excellent therapeutic efficacy of MDR S. aureus infection in vivo as well as negligible toxicity to cells and animals, indicating their potential use as antibacterial agents. This work provides a novel antibacterial strategy by combining the catalytic generation of ROS and NIR-II photothermal effect of nanozymes for efficient treatment of MDR bacteria-related infections.

A dual signal amplification strategy for the highly sensitive fluorescence detection of nucleic acids.

The development of convenient sensing probes and strategies for the highly sensitive and specific detection of biomolecules is greatly significant for the diagnosis of diseases. Herein, a dual signal amplification strategy comprising target-triggered recycling and duplex-specific nuclease (DSN)-mediated amplifications was designed and proposed for a highly sensitive fluorescence assay of nucleic acids. In this strategy, three special hairpin structured single-stranded DNAs (i.e., H1, H2 and H3) were designed, and target-triggered recycling was operated on H1-modified AuNPs (i.e., AuNP-H1 probes) in the presence of target DNA, H2 and H3 to form trefoil DNAs on AuNPs (i.e., AuNP-trefoil). DSN was then incubated with AuNP-trefoil to cleave the double-stranded trefoil DNAs, causing the ROX molecules labelled on H2 and H3 to fall off the AuNPs, which resulted in the recovery of the previous AuNP-quenched fluorescence signal of ROX. The sensing mechanism was confirmed by polyacrylamide gel electrophoresis and fluorescence characterizations, and the sensing strategy was optimized from several aspects, such as the MCH blocking time of the AuNP-H1 probes (20 min) and the concentration (0.3 U) and immobilization time (15 min) of DSN. The practicability of the probes and the dual signal amplification strategy was investigated by a fluorescence assay of target DNA in human serum. A good linear calibration curve from 50 fM to 100 pM was obtained with a low detection limit of 47.68 fM. The sensing strategy showed good specificity, which could efficiently distinguish the target DNA from the single-base mismatched (SM) and completely unmatched (UM) DNAs. The recovery values ranging from 91.85% to 106.3% with the relative standard deviations (RSD) less than 7.30% also illustrated the good reliability of the proposed sensing probes and strategy. The AuNP-H1 probes and dual signal amplification strategy provide highly effective diagnostic agents and method for the analysis of disease-related nucleic acid biomarkers at the molecular level for early disease detection.

Gut microbiota and lipid metabolism alterations in mice induced by oral cadmium telluride quantum dots.

The potential toxicity of cadmium-containing quantum dots (QDs) has received much attention because of increasing biomedical applications. However, little has been known about how cadmium telluride (CdTe) QDs influence the gut microbiota and lipid metabolism. In this study, mice were exposed orally to CdTe QDs (200 µL of 0.2, 2, 20 or 200 µm; twice per week) for 4 weeks. The oral experiments showed CdTe QD exposure led to a decrease of the Firmicutes/Bacteroidetes (F/B) ratio of gut microbiota, which highly negatively correlated with the low-density lipoprotein (LDL), triglyceride (TG) and total cholesterol (TC) levels in serum. In addition, the low-dose (0.2 and 2 µm) CdTe QDs significantly increased the diversity of gut microbiota, and did not elevate the LDL, TG and TC levels in serum. The medium dose (20 µm) of CdTe QDs caused the biggest decrease of the F/B ratio, so it significantly increased the LDL, TG and TC levels compared with the control. Furthermore, high-dose (200 µm) CdTe QDs caused various toxicities in the histopathology of liver and intestine, liver function and intestinal immunity, but did not significantly lead to changes of the LDL, TG and TC levels in serum. This study demonstrates that high-dose oral CdTe QDs mainly lead to tissue damage of the liver and intestine, while the medium and low doses of oral CdTe QDs induce shifts of gut microbiota structure, which are associated with blood lipid levels.

Single-Molecule Analysis of MicroRNA and Logic Operations Using a Smart Plasmonic Nanobiosensor.

Analysis of biomolecules at the single-molecule level is a great challenge in molecular diagnostics, gene profiling, and environmental monitoring. In this work, we design a smart plasmonic nanobiosensor based on individual Au@Ag core-shell nanocube (Au@Ag NC) modified with tetrahedron-structured DNA (tsDNA) for detecting microRNA 21 (miR-21) at the single-molecule level. An average localized surface plasmon resonance (LSPR) scattering spectral wavelength shift of approximately 0.4 nm can be obtained for a single miR-21 hybridization event on the nanobiosensor. In addition, the sensing mechanism of the individual Au@Ag NC is further verified by the three-dimensional finite-difference time-domain (3D-FDTD) simulations. Notably, this system not only allows the real-time detection of miR-21 with an aM level sensitivity over a large dynamic range from 1 aM to 1 nM, but also enables DNA-based logic operations as well as biomemory by exploiting miR-21, KpnI, and StuI-responsive assays. Our study opens a unique method for single-molecule detection of biomolecules and thus holds great promise in a variety of biological and biomedical applications.

Au nanoparticles on two-dimensional MoS2 nanosheets as a photoanode for efficient photoelectrochemical miRNA detection.

MiRNAs are small regulatory RNAs that play crucial roles in the oncogenic state in various cancers and have shown highly promising clinical applications as plasma-based markers for cancer classification and prognostication. Due to their electroanalytical advantages, photoelectrochemical biosensors are a very attractive alternative technology for miRNA sensing and detection. In this work, we demonstrated a novel photoelectrochemical (PEC) sensor using the in situ grown Au nanoparticles/two-dimensional molybdenum disulfide (MoS2) nanosheet heterojunction (MoS2-AuNPs) on ITO glass as the photoanode (MoS2-AuNPs/ITO). AuNPs were used as a photoelectronic transfer promoter and DNA probe immobilization carrier as well. The thiol modified biotin DNA with a hairpin structure was tethered to the MoS2-AuNPs/ITO surface to form a specific capturing layer for miRNA detection. The biotin specific protein streptavidin was used as the signal amplifying species. This PEC sensor is structurally simple and possesses sensitivity and specificity toward miRNA. The CV and EIS responses were evaluated to monitor the PEC anode fabrication. The stability and reproducibility of this PEC design strategy were both evaluated before it was used in analyzing the samples of miRNA in human serum. Finally, we found that this PEC sensor displayed a broad detection linear range and a low detection limit of 4.21 fM, and it can excellently discriminate the mismatched miRNA. These findings pave the way for developing PEC sensors targeting miRNA by using noble metals/MoS2 heterojunctions.

Poly-adenine-mediated fluorescent spherical nucleic acid probes for live-cell imaging of endogenous tumor-related mRNA.

Identification of tumor-related mRNA in living cells hold great promise for early cancer diagnosis and pathological research. Herein, we present poly-adenine (polyA)-mediated fluorescent spherical nucleic acid (FSNA) probes for intracellular mRNA detection with regulable sensitivities by programmably adjusting the loading density of DNA on gold nano-interface. Gold nanoparticles (AuNPs) functionalized with polyA-tailed recognition sequences were hybridized to fluorescent "reporter" strands to fabricate fluorescence-quenched FSNA probes. While exposed to target gene, the "reporter" strands were released from FSNA through strand displacement and fluorescence was recovered. With polyA20 tail as the attaching block, the detection limit of FSNA probes was calculated to be 0.31 nM, which is ~55 fold lower than that of thiolated probes without surface density regulation. Quantitative intracellular mRNA detection and imaging could be achieved with polyA-mediated FSNA probes within 2 hours, indicating their application potential in rapid and sensitive intracellular target imaging.

A Novel "Off-On" Fluorescent Probe Based on Carbon Nitride Nanoribbons for the Detection of Citrate Anion and Live Cell Imaging.

A novel fluorescent "off-on" probe based on carbon nitride (C3N4) nanoribbons was developed for citrate anion (C6H5O73-) detection. The fluorescence of C3N4 nanoribbons can be quenched by Cu2+ and then recovered by the addition of C6H5O73-, because the chelation between C6H5O73- and Cu2+ blocks the electron transfer between Cu2+ and C3N4 nanoribbons. The turn-on fluorescent sensor using this fluorescent "off-on" probe can detect C6H5O73- rapidly and selectively, showing a wide detection linear range (1~400 µM) and a low detection limit (0.78 µM) in aqueous solutions. Importantly, this C3N4 nanoribbon-based "off-on" probe exhibits good biocompatibility and can be used as fluorescent visualizer for exogenous C6H5O73- in HeLa cells.

Facile Synthesis of Yolk-Shell-Structured Triple-Hybridized Periodic Mesoporous Organosilica Nanoparticles for Biomedicine.

The synthesis of mesoporous nanoparticles with controllable structure and organic groups is important for their applications. In this work, yolk-shell-structured periodic mesoporous organosilica (PMO) nanoparticles simultaneously incorporated with ethane-, thioether-, and benzene-bridged moieties are successfully synthesized. The preparation of the triple-hybridized PMOs is via a cetyltrimethylammonium bromide-directed sol-gel process using mixed bridged silsesquioxanes as precursors and a following hydrothermal treatment. The yolk-shell-structured triple-hybridized PMO nanoparticles have large surface area (320 m(2) g(-1) ), ordered mesochannels (2.5 nm), large pore volume (0.59 cm(3) g(-1) ), uniform and controllable diameter (88-380 nm), core size (22-110 nm), and shell thickness (13-45 nm). In vitro cytotoxicity, hemolysis assay, and histological studies demonstrate that the yolk-shell-structured triple-hybridized PMO nanoparticles have excellent biocompatibility. Moreover, the organic groups in the triple-hybridized PMOs endow them with an ability for covalent connection of near-infrared fluorescence dyes, a high hydrophobic drug loading capacity, and a glutathione-responsive drug release property, which make them promising candidates for applications in bioimaging and drug delivery.

A new synthetic ligand that activates QscR and blocks antibiotic-tolerant biofilm formation in Pseudomonas aeruginosa.

Quorum sensing (QS) has been recognized to play an important role in many pathogenic bacteria and has become a novel target for the treatment of infectious disease. Pseudomonas aeruginosa is highly resistant to antibiotic treatment, largely due to its ability to form biofilms, and QS was found to be essential for the creation of mature, differentiated biofilms in this organism. A novel QS inhibitor, C2 (N-decanoyl-L-homoserine benzyl ester), can attenuate not only total protease and elastase activity, but also swarming motility and biofilm formation in the P. aeruginosa strain PAO1. We demonstrated that C2 showed a significant inhibitory effect on biofilm formation in a dose-dependent manner. Data from cDNA microarray showed that expression of 382 genes (∼6.4 %) was significantly different with C2 treatment, including downregulation of 215 genes (∼3.6 %) and upregulation of 167 genes (∼2.8 %). Real-time reverse transcription-polymerase chain reaction (RT-PCR) showed that the gene qscR, which encodes the LuxR-type receptor QscR (quorum sensing control repressor), was significantly upregulated by 375.4 % during C2 treatment. The mechanism by which C2 inhibits biofilm formation may be through repression of Las and Rhl systems by QscR. C2 was shown to reduce biofilm formation; in combination with antibiotics, it abolishes biofilm formation completely. This result may pave the way for new treatments for biofilm-related infections and may be exploited for the general prevention of biofilm formation.

Isolation of the autoinducer-quenching strain that inhibits LasR in Pseudomonas aeruginosa.

Quorum sensing (QS) has been recognized as a general phenomenon in microorganisms and plays an important role in many pathogenic bacteria. In this report, we used the Agrobacterium tumefaciens biosensor strain NT1 to rapidly screen for autoinducer-quenching inhibitors from bacteria. After initial screening 5389 isolates obtained from land and beach soil, 53 putative positive strains were identified. A confirmatory bioassay was carried out after concentrating the putative positive culture supernatant, and 22 strains were confirmed to have anti-LasR activity. Finally, we determined the strain JM2, which could completely inhibit biofilm formation of Pseudomonas aeruginosa PAO1, belonged to the genus Pseudomonas by analysis of 16S rDNA. Partially purified inhibitor factor(s) F5 derived from culture supernatants specifically inhibited LasR-controlled elastase and protease in wild type P. aeruginosa PAO1 by 68% and 73%, respectively, without significantly affecting growth; the rhl-controlled pyocyanin and rhamnolipids were inhibited by 54% and 52% in the presence of 100 µg/mL of F5. The swarming motility and biofilm of PAO1 were also inhibited by F5. Real time RT-PCR on samples from 100 µg/mL F5-treated P. aeruginosa showed downregulation of autoinducer synthase (LasRI and rhlI) and cognate receptor (lasR and rhlR) genes by 50%, 28%, 48%, and 29%, respectively. These results provide compelling evidence that the F5 inhibitor(s) interferes with the las system and significantly inhibits biofilm formation.

The recent advancements in protein nanoparticles for immunotherapy.

In recent years, the advancement of nanoparticle-based immunotherapy has introduced an innovative strategy for combatting diseases. Compared with other types of nanoparticles, protein nanoparticles have obtained substantial attention owing to their remarkable biocompatibility, biodegradability, ease of modification, and finely designed spatial structures. Nature provides several protein nanoparticle platforms, including viral capsids, ferritin, and albumin, which hold significant potential for disease treatment. These naturally occurring protein nanoparticles not only serve as effective drug delivery platforms but also augment antigen delivery and targeting capabilities through techniques like genetic modification and covalent conjugation. Motivated by nature's originality and driven by progress in computational methodologies, scientists have crafted numerous protein nanoparticles with intricate assembly structures, showing significant potential in the development of multivalent vaccines. Consequently, both naturally occurring and de novo designed protein nanoparticles are anticipated to enhance the effectiveness of immunotherapy. This review consolidates the advancements in protein nanoparticles for immunotherapy across diseases including cancer and other diseases like influenza, pneumonia, and hepatitis.

Emerging nanomaterials targeting macrophage adapted to abnormal metabolism in cancer and atherosclerosis therapy (Review).

Macrophages, as highly heterogeneous and plastic immune cells, occupy a pivotal role in both pro­inflammatory (M1) and anti­inflammatory (M2) responses. While M1­type macrophages secrete pro­inflammatory factors to initiate and sustain inflammation, M2­type macrophages promote inflammation regression and uphold tissue homeostasis. These distinct phenotypic transitions in macrophages are closely linked to significant alterations in cellular metabolism, encompassing key response pathways such as glycolysis, pentose phosphate pathway, oxidative phosphorylation, lipid metabolism, amino acid metabolism, the tricarboxylic acid cycle and iron metabolism. These metabolic adaptations enable macrophages to adapt their activities in response to varying disease microenvironments. Therefore, the present review focused primarily on elucidating the intricate metabolic pathways that underlie macrophage functionality. Subsequently, it offers a comprehensive overview of the current state­of­the­art nanomaterials, highlighting their promising potential in modulating macrophage metabolism to effectively hinder disease progression in both cancer and atherosclerosis.

Mitochondria-Targeting and Oxygen Self-Supplying Eccentric Hollow Nanoplatform for Enhanced Breast Cancer Photodynamic Therapy.

Photodynamic therapy (PDT) has received increasing attention for tumor therapy due to its minimal invasiveness and spatiotemporal selectivity. However, the poor targeting of photosensitizer and hypoxia of the tumor microenvironment limit the PDT efficacy. Herein, eccentric hollow mesoporous organic silica nanoparticles (EHMONs) are prepared by anisotropic encapsulation and hydrothermal etching for constructing PDT nanoplatforms with targeting and hypoxia-alleviating properties. The prepared EHMONs possess a unique eccentric hollow structure, a uniform size (300 nm), a large cavity, and ordered mesoporous channels (2.3 nm). The EHMONs are modified with the mitochondria-targeting molecule triphenylphosphine (CTPP) and photosensitizers chlorin e6 (Ce6). Oxygen-carrying compound perfluorocarbons (PFCs) are further loaded in the internal cavity of EHMONs. Hemolytic assays and in vitro toxicity experiments show that the EHMONs-Ce6-CTPP possesses very good biocompatibility and can target mitochondria of triple-negative breast cancer, thus increasing the accumulation of photosensitizers Ce6 at mitochondria after entering cancer cells. The EHMONs-Ce6-CTPP@PFCs with oxygen-carrying ability can alleviate hypoxia after entering in the cancer cell. Phantom and cellular experiments show that the EHMONs-Ce6-CTPP@PFCs produce more singlet oxygen reactive oxygen species (ROSs). Thus, in vitro and in vivo experiments demonstrated that the EHMONs-Ce6-CTPP@PFCs showed excellent treatment effects for triple-negative breast cancer. This research provides a new method for a targeting and oxygen-carrying nanoplatform for enhancing PDF effectiveness.

Programmed Nanocloak of Commensal Bacteria-Derived Nanovesicles Amplify Strong Immunoreactivity against Tumor Growth and Metastatic Progression.

Recent discoveries in commensal microbiota demonstrate the great promise of intratumoral bacteria as attractive molecular targets of tumors in improving cancer treatment. However, direct leveraging of in vivo antibacterial strategies such as antibiotics to potentiate cancer therapy often leads to uncertain effectiveness, mainly due to poor selectivity and potential adverse effects. Here, building from the clinical discovery that patients with breast cancer featured rich commensal bacteria, we developed an activatable biointerface by encapsulating commensal bacteria-derived extracellular vesicles (BEV) with a responsive nanocloak to potentiate immunoreactivity against intratumoral bacteria and breast cancer. We show that the interfacially cloaked BEV (cBEV) not only overcame serious systemic side responses but also demonstrated heightened immunogenicity by intercellular responsive immunogenicity, facilitating dendritic cell maturation through activating the cGAS-STING pathway. As a preventive measure, vaccination with nanocloaked cBEVs achieved strong protection against bacterial infection, largely providing prophylactic efficiency against tumor challenges. When treated in conjunction with immune checkpoint inhibitor anti-PD-L1 antibodies, the combined approach elicited a potent tumor-specific immune response, synergistically inhibiting tumor progression and mitigating lung metastases.