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Artificially engineered bacteria to treat gastrointestinal disease and cancer

DRUG DISCOVERY TODAY (2023)

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Article Chemistry, Multidisciplinary

Prodrug Integrated Envelope on Probiotics to Enhance Target Therapy for Ulcerative Colitis

Kun Zhang et al.

Summary: Ulcerative colitis (UC), a disease affecting millions of patients worldwide, is associated with gut microbiota disorders. Probiotics-based therapy is considered as an effective intervention for UC. In this study, a bioengineered probiotic decorated with a multifunctional prodrug coating was developed to address the limitations of current oral probiotics delivery. The results showed that this engineered probiotic was able to protect gut microbes, release drugs in the colon, prolong drug retention, and regulate inflammation, thereby providing a potential therapeutic strategy for UC treatment.

ADVANCED SCIENCE (2023)

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Article Chemistry, Multidisciplinary

Integrating Bacteria with a Ternary Combination of Photosensitizers for Monochromatic Irradiation-Mediated Photoacoustic Imaging-Guided Synergistic Photothermal Therapy

Haiyan Guo et al.

Summary: Photosensitizer-based therapy faces limitations such as weak and easily attenuated photosensitive effects, poor tumor penetration and retention, and the need for multiple irradiation. In this study, bacteria were engineered to express melanin and coated with synthetic photosensitizers, forming a ternary combination for photoacoustic imaging-guided photothermal therapy. The integrated bacteria exhibited stable triple photoacoustic and photothermal effects under monochromatic irradiation, and were able to preferentially colonize hypoxic tumor tissue and generate uniform imaging signals and sufficient heating upon laser irradiation. The results showed inhibited tumor growth and extended survival in different tumor-bearing mouse models, suggesting the potential of bacteria-based innovative photosensitizers for imaging-guided therapy.

ACS NANO (2023)

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Article Chemistry, Multidisciplinary

Inorganic Nanosheet-Shielded Probiotics: A Self-Adaptable Oral Delivery System for Intestinal Disease Treatment

Ya-Xuan Zhu et al.

Summary: In this study, a copolymer-modified two-dimensional H-silicene nanomaterial was developed to help probiotics adapt to different gastrointestinal microenvironments. The material can resist acidic destruction in the stomach and generate anti-inflammatory hydrogen gas in the intestine, thus alleviating colitis. This strategy holds great significance for the development of intelligent self-adaptive materials.

NANO LETTERS (2023)

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Article Nanoscience & Nanotechnology

Artificial-enzymes-armed Bifidobacterium longum probiotics for alleviating intestinal inflammation and microbiota dysbiosis

Fangfang Cao et al.

Summary: Combining artificial enzymes with probiotics, modified probiotics are used to treat inflammatory bowel disease, overcoming limitations of traditional treatments and showing promising outcomes.

NATURE NANOTECHNOLOGY (2023)

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Article Microbiology

Biomarker-responsive engineered probiotic diagnoses, records, and ameliorates inflammatory bowel disease in mice

Zhen -Ping Zou et al.

Summary: Engineered probiotic i-ROBOT has been developed to noninvasively monitor and record the occurrence and progression of inflammatory bowel disease (IBD) in real time, and release treatments based on disease-associated biomarkers. It provides a heritable genomic DNA sequence and a colorimetric signal by activating a base-editing system in response to the inflammatory marker thiosulfate. In experiments with mice, i-ROBOT effectively ameliorated colitis and showed potential for the treatment of gastrointestinal and metabolic disorders.

CELL HOST & MICROBE (2023)

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Article Chemistry, Multidisciplinary

Engineered Bacteria for Enhanced Radiotherapy against Breast Carcinoma

Pei Pan et al.

Summary: In this study, an integrated nanosystem composed of engineered bacteria and nanoparticles was developed for sensitizing radiotherapy. The system could target tumor sites and release a radiosensitizer, enhancing the effectiveness of radiotherapy.

ACS NANO (2022)

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Article Chemistry, Multidisciplinary

Self-Blockade of PD-L1 with Bacteria-Derived Outer-Membrane Vesicle for Enhanced Cancer Immunotherapy

Jingmei Pan et al.

Summary: A nanocarrier that achieves self-blockade of PD-L1 in tumor cells and a detection kit to quantitatively measure the binding rate of PD-1/PD-L1 have been developed, improving the efficacy of PD-1/PD-L1 self-blocking therapy.

ADVANCED MATERIALS (2022)

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Article Chemistry, Multidisciplinary

Polydopamine Nanoparticle-Mediated Dopaminergic Immunoregulation in Colitis

Juanjuan Li et al.

Summary: The study explores the use of the dopaminergic system to suppress hyperactive immune responses and synthesizes a polydopamine nanoparticular immunosuppressant. It shows that the immunosuppressant can regulate T cell balance and be combined with gut microbiota modulation to treat inflammation effectively.

ADVANCED SCIENCE (2022)

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Article Multidisciplinary Sciences

A single-cell nanocoating of probiotics for enhanced amelioration of antibiotic-associated diarrhea

Jiezhou Pan et al.

Summary: The authors developed a polyphenol-based nanoarmor coating that protects probiotics from antibiotics and enhances their effectiveness against antibiotic-mediated diarrhea. The nanoarmor absorbs antibiotic molecules and allows the bacteria to colonize in the gastrointestinal tract, reducing diarrhea and inflammation caused by antibiotics.

NATURE COMMUNICATIONS (2022)

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Article Engineering, Biomedical

Enhancing the tropism of bacteria via genetically programmed biosensors

Tiffany Chien et al.

Summary: The tropism of engineered bacteria in vivo can be enhanced by genetic circuits, linked by AND-gate logic, that couple bacterial sensing and growth. Engineered bacteria for therapeutic applications would benefit from control mechanisms that confine the growth of the bacteria within specific tissues or regions in the body. Multiplexing of genetic circuits may enhance the localization of bacteria to specified niches, providing increased specificity for therapeutic applications.

NATURE BIOMEDICAL ENGINEERING (2022)

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Article Engineering, Biomedical

Dual drugs decorated bacteria irradiate deep hypoxic tumor and arouse strong immune responses

Wenfei Chen et al.

Summary: This study demonstrates the successful use of engineered Salmonella bacteria with modified surface to achieve targeted photothermal therapy and magnified immunotherapy in tumor tissues. The synergistic strategy stimulates the immune system from multiple dimensions, leading to effective prevention and inhibition of tumor growth.

BIOMATERIALS (2022)

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Review Multidisciplinary Sciences

Engineering bacteria as interactive cancer therapies

Candice R. Gurbatri et al.

Summary: With the use of synthetic biology tools, researchers are repurposing bacteria as tumor-specific delivery systems, which can modulate the tumor microenvironment and enhance therapeutic efficacy and safety through their immunogenicity and local payload production.

SCIENCE (2022)

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Article Chemistry, Multidisciplinary

Multimodal oncolytic bacteria by coating with tumor cell derived nanoshells

Rui Liu et al.

Summary: This study describes the development of carcinoma cell-mimetic bacteria (CCMB), which are bacteria coated with tumor cell-derived nanoshells, to enhance their tumor-targeting and therapeutic capabilities. The CCMB exhibit low inflammatory reaction, prolonged survival in the body, tumor-specific localization, and dual modality of antigen-specific immunotherapy and microbial therapy.

NANO TODAY (2022)

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Article Multidisciplinary Sciences

Spatiotemporal control of engineered bacteria to express interferon-γ by focused ultrasound for tumor immunotherapy

Yuhao Chen et al.

Summary: The authors designed an ultrasound-responsive bacterium to release the immune regulatory molecule IFN-γ at the tumor site, promoting anti-tumor immune responses. This approach solves the challenge of controlling gene expression in the tumor site and provides a new strategy for bacteria-mediated tumor immunotherapy.

NATURE COMMUNICATIONS (2022)

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Article Multidisciplinary Sciences

Bacteria loaded with glucose polymer and photosensitive ICG silicon-nanoparticles for glioblastoma photothermal immunotherapy

Rong Sun et al.

Summary: The authors have developed a bacteria-based drug delivery system for the treatment of glioblastoma. This system bypasses the blood-brain barrier and uses photothermal therapy and immune responses to destroy bacteria-infected glioblastoma cells and prolong the survival of mice. The residual bacteria can also be effectively eliminated from the body.

NATURE COMMUNICATIONS (2022)

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Article Pharmacology & Pharmacy

Bimodal Imaging of Tumors via Genetically Engineered Escherichia coli

Linlin Zhang et al.

Summary: A dual-modal imaging tumor-homing bacteria (GVs-miRFP680 MG1655) has been developed, allowing optical and acoustic imaging capabilities in vivo. The engineered bacteria effectively integrate the advantages of near-infrared fluorescent proteins and gas vesicles for imaging, with signals lasting up to 25 minutes and 96 hours, respectively. The combination of different imaging modalities in tumor-homing bacteria may contribute to non-invasive monitoring of the therapeutic effect of bacterial therapy in the future.

PHARMACEUTICS (2022)

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Article Engineering, Biomedical

Bacterial-based cancer therapy: An emerging toolbox for targeted drug/gene delivery

Dewu Lin et al.

Summary: Bacteria are increasingly being considered for targeted tumor therapy due to their intrinsic tumor tropism and ability to rapidly colonize in the favorable TME. Compared to other nano-strategies, tumor-targeting bacteria are largely unaffected by the tumor cells and microenvironment. Integration of live bacteria with anti-cancer drugs and nanomaterials can enhance targeted delivery and accumulation in tumors.

BIOMATERIALS (2021)

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Review Engineering, Biomedical

Genetically engineered oncolytic bacteria as drug delivery systems for targeted cancer theranostics

Yu Chen et al.

Summary: Drug delivery systems based on genetically engineered oncolytic bacteria have unique properties that enable them to target tumor tissues and suppress tumor growth effectively, showing potential value for clinical applications. By integrating oncolytic bacteria into cancer therapies, novel strategies are being developed to improve and standardize current treatment regimens in the near future.

ACTA BIOMATERIALIA (2021)

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Article Chemistry, Multidisciplinary

Polymerization-Mediated Multifunctionalization of Living Cells for Enhanced Cell-Based Therapy

Chao Pan et al.

Summary: A versatile approach for decorating living cells with multimodal coatings is reported, enabling enhanced cell-based therapy by tuning cell behaviors. The dual cytoprotective and targeting effects of these coatings significantly improve the bioavailability and accumulation of decorated cells, leading to increased treatment efficacy in colitis mice. Decorating cells with multifunctional coatings provides a robust platform for developing enhanced cell-based therapy.

ADVANCED MATERIALS (2021)

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Review Biochemical Research Methods

Bacteriophage Capsid Modification by Genetic and Chemical Methods

Caitlin M. Carmody et al.

Summary: Bacteriophages are versatile viruses with potential applications in agriculture and public health. Their capsids can be modified genetically or chemically to enhance specificity and stability for various functions.

BIOCONJUGATE CHEMISTRY (2021)

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Article Multidisciplinary Sciences

Metabolic modulation of tumours with engineered bacteria for immunotherapy

Fernando P. Canale et al.

Summary: Engineered bacteria were developed to convert ammonia to l-arginine in tumors, increasing intratumoral l-arginine concentrations, T cell infiltration, and synergistic effects with PD-L1 blocking antibodies in tumor clearance. These results indicate that microbial therapies can enhance immunotherapy efficacy by modulating the tumor microenvironment.

NATURE (2021)

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Article Chemistry, Multidisciplinary

Antibody Engineered Platelets Attracted by Bacteria-Induced Tumor-Specific Blood Coagulation for Checkpoint Inhibitor Immunotherapy

Jin-Xuan Fan et al.

Summary: Escherichia coli TOP10 can induce rapid and intense blood coagulation in tumor tissues, recruiting macrophages that are polarized to an anti-tumor M1-like phenotype. Platelets decorated with CD47 antibodies are used to promote the phagocytosis of polarized macrophages for tumor cells. This manipulation of local blood coagulation in tumors shows potential for delivering immune checkpoint inhibitors and enhancing tumor immunotherapy.

ADVANCED FUNCTIONAL MATERIALS (2021)

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Review Microbiology

Modifications of cell wall polymers in Gram-positive bacteria by multi-component transmembrane glycosylation systems

Jeanine Rismondo et al.

Summary: This article provides a brief overview of the functions and complexity of secondary cell wall polymers in Gram-positive bacteria, focusing on the biosynthesis pathways of teichoic acid and complex polysaccharides, as well as the recent glycosylation mechanism.

CURRENT OPINION IN MICROBIOLOGY (2021)

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Article Chemistry, Multidisciplinary

Photoelectric Bacteria Enhance the In Situ Production of Tetrodotoxin for Antitumor Therapy

Xia-Nan Wang et al.

Summary: The study introduced an optically controlled material-assisted microbial system that enhances the synthesis of antitumor drugs at tumor sites by biosynthesizing gold nanoparticles on bacterial surface. This system has the potential to provide a promising antitumor therapy strategy with improved drug synthesis efficiency in situ.

NANO LETTERS (2021)

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Article Chemistry, Medicinal

Gut Microbe-Derived Outer Membrane Vesicles: A Potential Platform to Control Cecal Load of Campylobacter jejuni

Ankita Singh et al.

Summary: Acute diarrheal illness and gastroenteritis caused by Campylobacter jejuni infection are significant public health risks, especially in children under five in developing countries. Limited genetic diversity among Campylobacter jejuni and understanding of host immunity are obstacles to developing effective measures to control infection. Utilizing bacterial outer-membrane vesicles as vaccine targets shows promise in inducing specific immune responses against Campylobacter jejuni.

ACS INFECTIOUS DISEASES (2021)

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Article Multidisciplinary Sciences

Mucosal immunity-mediated modulation of the gut microbiome by oral delivery of probiotics into Peyer's patches

Sisi Lin et al.

Summary: The oral delivery of camouflaged probiotics can induce mucosal immune responses, regulate the gut microbiota, maintain gut homeostasis, and provide defense against external threats. Studies show that this approach effectively prevents intestinal barrier breakdown, bacterial translocation, and systemic inflammation.

SCIENCE ADVANCES (2021)

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Article Food Science & Technology

Efficient chemical hydrophobization of lactic acid bacteria-One-step formation of double emulsion

Xiaoyi Jiang et al.

Summary: This study successfully hydrophobically modified the surface of Lactobacillus bacteria using lauroyl chloride, resulting in higher hydrophobicity in forming double emulsions. High concentrations of lauroyl chloride led to rapid autoaggregation of bacteria in aqueous solution, but with minimal impact on the instantaneous culturability of the modified bacteria.

FOOD RESEARCH INTERNATIONAL (2021)

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Article Chemistry, Multidisciplinary

Bacteria-Mediated Tumor Therapy via Photothermally-Programmed Cytolysin A Expression

Longyu Wang et al.

Summary: By utilizing bacteria to express therapeutic protein and constructing a thermally-activated biohybrid with gold nanoparticles on the bacterial surface, a photothermal therapy targeting tumors is achieved. This treatment modality results in tumor cell destruction through NIR laser-induced heat production. Both in vitro and in vivo experiments confirm the effectiveness of this therapy in inhibiting tumor cell proliferation.

SMALL (2021)

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Article Chemistry, Multidisciplinary

Decorating Bacteria with a Therapeutic Nanocoating for Synergistically Enhanced Biotherapy

Weiliang Hou et al.

Summary: Combining probiotics with therapeutic nanocoatings can enhance biotherapy synergistically. Silk fibroin nanocoating provides bacteria with improved survival rates and enhanced therapeutic effects.

SMALL (2021)

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Article Cell Biology

NIR light-responsive bacteria with live bio-glue coatings for precise colonization in the gut

Meihui Cui et al.

Summary: Recombinant bacterial colonization is essential in disease prevention, alleviation, and treatment, with the success of application hinges on efficient spatiotemporal colonization of host gut. The use of engineered upconversion microgels and light-responsive bacteria in this study demonstrated controlled and effective colonization of EcN, which successfully alleviated DSS-induced colitis in mice, potentially advancing the clinical application of engineered microbial therapeutics.

CELL REPORTS (2021)

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Review Pharmacology & Pharmacy

Escherichiacoli Nissle 1917 as a Novel Microrobot for Tumor-Targeted Imaging and Therapy

Qingyao Liu et al.

Summary: Escherichia coli Nissle 1917 (EcN) demonstrates promising potential as a drug delivery system for tumor treatment due to its facultative anaerobic property that allows it to selectively colonize in the hypoxic area of tumors. By engineering EcN as a bacteria-based microrobot, it can be utilized for molecular imaging, drug delivery, and gene delivery in cancer therapy.

PHARMACEUTICS (2021)

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Article Materials Science, Biomaterials

Layer-by-layer assembly of Au and CdS nanoparticles on the surface of bacterial cells for photo-assisted bioanodes in microbial fuel cells

Pingping Li et al.

Summary: Utilizing the electrostatic layer-by-layer assembly strategy, conductive Au nanoparticles and photo-responsive CdS nanoparticles were alternately modified onto the surface of Escherichia coli for photo-assisted bioanodes in microbial fuel cells. The CdS layer was found to protect the bacterial cells from light-induced inactivation, while the outer layer of Au nanoparticles served as a conductive channel for electron transfer.

JOURNAL OF MATERIALS CHEMISTRY B (2021)

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Article Biochemistry & Molecular Biology

Combination of attenuated Salmonella carrying PD-1 siRNA with nifuroxazide for colon cancer therapy

Tiesuo Zhao et al.

JOURNAL OF CELLULAR BIOCHEMISTRY (2020)

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Article Chemistry, Multidisciplinary

Self-Mineralized Photothermal Bacteria Hybridizing with Mitochondria-Targeted Metal-Organic Frameworks for Augmenting Photothermal Tumor Therapy

Qi-Wen Chen et al.

ADVANCED FUNCTIONAL MATERIALS (2020)

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Article Cell Biology

Engineered probiotics for local tumor delivery of checkpoint blockade nanobodies

Candice R. Gurbatri et al.

SCIENCE TRANSLATIONAL MEDICINE (2020)

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Article Nanoscience & Nanotechnology

Liquid Metal Hybrid Platform-Mediated Ice-Fire Dual Noninvasive Conformable Melanoma Therapy

Yi Hou et al.

ACS APPLIED MATERIALS & INTERFACES (2020)

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Article Chemistry, Multidisciplinary

On-Demand Bacterial Reactivation by Restraining within a Triggerable Nanocoating

Pingping Feng et al.

ADVANCED MATERIALS (2020)

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Article Chemistry, Multidisciplinary

Inhibition of Tumor Progression through the Coupling of Bacterial Respiration with Tumor Metabolism

Qi-Wen Chen et al.

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION (2020)

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Article Biology

Upconversion optogenetic micro-nanosystem optically controls the secretion of light-responsive bacteria for systemic immunity regulation

Chun Yang et al.

COMMUNICATIONS BIOLOGY (2020)

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Article Materials Science, Biomaterials

AttenuatedSalmonella typhimurium-mediated tumour targeting imaging based on peptides

Saisai Xiong et al.

BIOMATERIALS SCIENCE (2020)

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Article Cell Biology

Bioengineering commensal bacteria-derived outer membrane vesicles fordelivery of biologics to the gastrointestinal and respiratory tract

Ana L. Carvalho et al.

JOURNAL OF EXTRACELLULAR VESICLES (2019)

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Article Multidisciplinary Sciences

Camouflaging bacteria by wrapping with cell membranes

Zhenping Cao et al.

NATURE COMMUNICATIONS (2019)

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Article Chemistry, Multidisciplinary

Bio-Orthogonal Bacterial Reactor for Remission of Heavy Metal Poisoning and ROS Elimination

Pei Pan et al.

ADVANCED SCIENCE (2019)

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Article Chemistry, Multidisciplinary

Engineered Bacterial Bioreactor for Tumor Therapy via Fenton-Like Reaction with Localized H2O2 Generation

Jin-Xuan Fan et al.

ADVANCED MATERIALS (2019)

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Article Multidisciplinary Sciences

Biointerfacial self-assembly generates lipid membrane coated bacteria for enhanced oral delivery and treatment

Zhenping Cao et al.

NATURE COMMUNICATIONS (2019)

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Article Biotechnology & Applied Microbiology

Thickness of Polyelectrolyte Layers of Separately Confined Bacteria Alters Key Physiological Parameters on a Single Cell Level

Iaroslav Rybkin et al.

FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY (2019)

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Article Multidisciplinary Sciences

Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients

V. Gopalakrishnan et al.

SCIENCE (2018)

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Article Chemistry, Multidisciplinary

Bacteria-Driven Hypoxia Targeting for Combined Biotherapy and Photothermal Therapy

Wenfei Chen et al.

ACS NANO (2018)

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Article Multidisciplinary Sciences

The commensal microbiome is associated with anti-PD-1 efficacy in metastatic melanoma patients

Vyara Matson et al.

SCIENCE (2018)

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Optically-controlled bacterial metabolite for cancer therapy

Di-Wei Zheng et al.

NATURE COMMUNICATIONS (2018)

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Article Food Science & Technology

Encapsulation of Lactobacillus casei into Calcium Pectinate-Chitosan Beads for Enteric Delivery

Aigerim Bepeyeva et al.

JOURNAL OF FOOD SCIENCE (2017)

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Bacterial outer membrane vesicles suppress tumor by interferon-γ- mediated antitumor response

Oh Youn Kim et al.

NATURE COMMUNICATIONS (2017)

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Article Chemistry, Applied

The smaller, the better? The size effect of alginate beads carrying plant growth-promoting bacteria for seed coating

Teresa Berninger et al.

JOURNAL OF MICROENCAPSULATION (2016)

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Article Chemistry, Multidisciplinary

Bacteria-Mediated Hypoxia-Specific Delivery of Nanoparticles for Tumors Imaging and Therapy

Cheng-Hung Luo et al.

NANO LETTERS (2016)

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Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy

Ayelet Sivan et al.

SCIENCE (2015)

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Article Cell Biology

Programmable probiotics for detection of cancer in urine

Tal Danino et al.

SCIENCE TRANSLATIONAL MEDICINE (2015)

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Salmonella: A review on pathogenesis, epidemiology and antibiotic resistance

Shu-Kee Eng et al.

FRONTIERS IN LIFE SCIENCE (2015)

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Article Agriculture, Multidisciplinary

Enhanced Survival of Probiotic Lactobacillus acidophilus by Encapsulation with Nanostructured Polyelectrolyte Layers through Layer-by-Layer Approach

Angel J. Priya et al.

JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY (2011)

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Microencapsulation of Live Probiotic Bacteria

Mohammad Ariful Islam et al.

JOURNAL OF MICROBIOLOGY AND BIOTECHNOLOGY (2010)

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Living Fungi Cells Encapsulated in Polyelectrolyte Shells Doped with Metal Nanoparticles

Rawil F. Fakhrullin et al.

LANGMUIR (2009)

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