Bacterial therapies at the interface of synthetic biology and nanomedicine

Nature Reviews Bioengineering, Journal Year: 2023, Volume and Issue: 2(2), P. 120 - 135

Published: Oct. 10, 2023

Language: Английский

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Upconversion dual-photosensitizer–expressing bacteria for near-infrared monochromatically excitable synergistic phototherapy

Science Advances, Journal Year: 2024, Volume and Issue: 10(10)

Published: March 6, 2024

Synergistic phototherapy stands for superior treatment prospects than a single phototherapeutic modality. However, the combined photosensitizers often suffer from incompatible excitation mode, limited irradiation penetration depth, and lack of specificity. We describe development upconversion dual-photosensitizer-expressing bacteria (UDPB) near-infrared monochromatically excitable combination phototherapy. UDPB are prepared by integrating genetic engineering surface modification, in which encoded to simultaneously express photothermal melanin phototoxic KillerRed protein primary amino groups derived free thiols biorthogonal conjugation nanoparticles. exhibit monochromatic irradiation-mediated dual-activation characteristic as conversion can be initiated directly, while photodynamic effect stimulated indirectly upconverted visible light emission. also show living features colonize hypoxic lesion sites inhibit pathogens via bacterial community competition. In two murine models solid tumor skin wound infection, separately induce robust antitumor response rapid healing effect.

Language: Английский

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Hyperbaric oxygen enhances tumor penetration and accumulation of engineered bacteria for synergistic photothermal immunotherapy

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: June 17, 2024

Abstract Bacteria-mediated cancer therapeutic strategies have attracted increasing interest due to their intrinsic tumor tropism. However, bacteria-based drugs face several challenges including the large size of bacteria and dense extracellular matrix, limiting intratumoral delivery efficiency. In this study, we find that hyperbaric oxygen (HBO), a noninvasive method, can effectively deplete matrix thus enhance bacterial accumulation within tumors. Inspired by finding, modify Escherichia coli Nissle 1917 (EcN) with cypate molecules yield EcN-cypate for photothermal therapy, which subsequently induce immunogenic cell death (ICD). Importantly, HBO treatment significantly increases facilitates infiltration immune cells realize desirable eradication through therapy ICD-induced immunotherapy. Our work provides facile strategy efficiency natural/engineered bacteria, may promote clinical translation bacteria-mediated synergistic therapy.

Language: Английский

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Innovative Applications of Bacteria and Their Derivatives in Targeted Tumor Therapy

ACS Nano, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 28, 2025

Despite significant progress in cancer treatment, traditional therapies still face considerable challenges, including poor targeting, severe toxic side effects, and the development of resistance. Recent advances biotechnology have revealed potential bacteria their derivatives as drug delivery systems for tumor therapy by leveraging biological properties. Engineered bacteria, Escherichia coli, Salmonella, Listeria monocytogenes, along with derivatives─outer membrane vesicles (OMVs), bacterial ghosts (BGs), spores (BSPs)─can be loaded a variety antitumor agents, enabling precise targeting sustained release within microenvironment (TME). These possess intrinsic properties that stimulate immune system, enhancing both innate adaptive responses to further amplify therapeutic effects. The ability naturally accumulate hypoxic regions versatility genetic modifications allow tailored strategies synergistically enhance effectiveness chemotherapy, immunotherapy, targeted therapies. This review comprehensively examines fundamental principles therapy, focusing on employed engineering, loading, use therapy. It also discusses challenges faced optimizing systems, such safety concerns, unintended responses, scalability clinical applications. By exploring these aspects, this provides theoretical framework improving bacterial-based contributing more effective personalized treatments.

Language: Английский

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Bioactive Bacteria/MOF Hybrids Can Achieve Targeted Synergistic Chemotherapy and Chemodynamic Therapy against Breast Tumors

Advanced Functional Materials, Journal Year: 2023, Volume and Issue: 33(42)

Published: July 3, 2023

Abstract The hypoxic tumor microenvironment (TME) significantly affects cancer treatment. Conventional chemotherapeutic agents cannot effectively target tissue, which decreases efficacy and results in severe toxic side effects. To alleviate this problem, a self‐driving biomotor is developed by functionalizing MCDP nanoparticles containing calcium peroxide doxorubicin (DOX) loaded onto polydopamine‐coated metal–organic frameworks（MOF）, with the anaerobic Bifidobacterium infantis (Bif) for synergistic chemotherapy chemodynamic therapy (CDT) against breast cancer. materials of institute Lavoisier (MIL) frameworks + CaO 2 DOX polydopamine (MCDP)@Bif biohybrid actively targets regions solid tumors via inherent targeting ability Bif. Once it has accumulated generates hydroxyl radicals through enhanced Fenton‐type reactions between Fe 2+ self‐generated hydrogen acidic TME. disruption Ca homeostasis resulting mitochondrial overload triggers apoptosis enhances oxidative stress, promoting cell death. found that concentration MCDP@Bif‐treated 3.8 times higher than free‐DOX‐treated tumors, prolongs median survival tumor‐bearing mice to 69 days reduces effects DOX. Therefore, novel bacteria‐driven drug delivery system highly effective achieving CDT tumors.

Language: Английский

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Dopamine Polymerization-Mediated Surface Functionalization toward Advanced Bacterial Therapeutics

Accounts of Chemical Research, Journal Year: 2024, Volume and Issue: 57(6), P. 945 - 956

Published: Feb. 29, 2024

ConspectusBacteria-based therapy has spotlighted an unprecedented potential in treating a range of diseases, given that bacteria can be used as both drug vehicles and therapeutic agents. However, the use for disease treatment often suffers from unsatisfactory outcomes, due largely to their suboptimal bioavailability, dose-dependent toxicity, low targeting colonization. In past few years, substantial efforts have been devoted tackling these difficulties, among which methods capable integrating with multiple functions extensively pursued. Different conventional genetic engineering modern synthetic bioengineering, surface modification emerged simple yet flexible strategy introduce different functional motifs. Polydopamine, easily formed via situ dopamine oxidation self-polymerization, is appealing biomimetic polymer widely applied interfacial functionalization. By virtue its catechol groups, polydopamine efficiently codeposited multitude elements on diverse surfaces.In this Account, we summarize recent advances our group focus polymerization-mediated functionalization advanced microbial therapy. First, present optimized bacterial under cytocompatible conditions by polymerization. Taking advantage hydrogen bonding, π–π stacking, Michael addition, Schiff base reaction polydopamine, small molecules macromolecules are facilely onto surface. Namely, monomodal, dual-modal, multimodal achieved self-deposition, codeposition unitary composition, set components, respectively. Second, outline regulation modification. The endows ability resist vivo insults, such gastrointestinal tract stressors immune clearance, resulting greatly improved bioavailability. Integration specific ligands or components enables modified increase accumulation colonization at lesion sites play synergistic effects treatment. Bacteria bioactive moieties, protein antigens, antibodies, immunoadjuvants, even able actively interact host, particularly elicit responses either suppressing overactivation promote reversion pathological inflammations provoking protective innate and/or adaptive immunity inhibit pathogenic invaders. Third, highlight applications surface-modified multifunctional living therapeutics treatment, especially alleviating inflammatory bowel diseases oral delivery intervening types cancer through systemic intratumoral injection. Finally, discuss challenges prospects multifunctionalization preparing well bench bedside translation. We anticipate Account provide insightful overview inspire innovative thinking new develop next-generation various diseases.

Language: Английский

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Image‐Guided Photothermal and Immune Therapy of Tumors via Melanin‐Producing Genetically Engineered Bacteria

Small, Journal Year: 2024, Volume and Issue: 20(26)

Published: Feb. 17, 2024

Abstract Photothermal therapy (PTT) is a new treatment modality for tumors. However, the efficient delivery of photothermal agents into tumors remains difficult, especially in hypoxic tumor regions. In this study, an approach to deliver melanin, natural agent, using genetically engineered bacteria image‐guided and immune developed. An Escherichia coli MG1655 transformed with recombinant plasmid harboring tyrosinase gene produce melanin nanoparticles. Melanin‐producing (MG1655‐M) are systemically administered 4T1 tumor‐bearing mice. The tumor‐targeting properties MG1655‐M environment integrate hypoxia targeting, photoacoustic imaging, therapeutic “all‐in‐one” manner. This eliminates need post‐modification achieve hypoxia‐targeted cancer therapy. Tumor growth significantly suppressed by irradiating 808 nm laser. Furthermore, strong antitumor immunity triggered PTT, thereby producing long‐term memory effects that effectively inhibit metastasis recurrence. work proposes guided melanin‐producing bacteria, which can offer broad potential applications treatment.

Language: Английский

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Single-cell encapsulation systems for probiotic delivery: Armor probiotics

Advances in Colloid and Interface Science, Journal Year: 2024, Volume and Issue: 332, P. 103270 - 103270

Published: Aug. 6, 2024

Language: Английский

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Engineering a monitoring-therapeutic in situ hydrogel via a cellulose-integrated nanointerface

Chemical Engineering Journal, Journal Year: 2024, Volume and Issue: 482, P. 149015 - 149015

Published: Jan. 26, 2024

Language: Английский

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Macroencapsulated bacteria for in vivo sensing and therapeutics

Matter, Journal Year: 2024, Volume and Issue: 7(4), P. 1440 - 1465

Published: Feb. 26, 2024

Language: Английский

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