Filamentous bacteriophages, natural nanoparticles, for viral vaccine strategies

wang, yicun; Zhang, Guangxin; Zhong, Lili; Qian, Min; Wang, Meng; Cui, Ranji

doi:10.1039/d1nr08064d

Cited by 7 publications

(4 citation statements)

References 155 publications

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“…Fd phages , specific to bacterial hosts, do not infect or harm mammalian cells and are remarkably stable under a range of environmental conditions, rendering them ideal for diagnostic applications (Wang et al 2022 ). Furthermore, fd phages can be easily propagated and produced in large quantities, facilitating the development of cost-effective and scalable diagnostic assays (Daubie et al 2022 ; González-Mora et al 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Advanced detection of cervical cancer biomarkers using engineered filamentous phage nanofibers

Zhou,

Wang,

Bao

et al. 2024

Appl Microbiol Biotechnol

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Cervical cancer is a major global health concern, characterized by its high incidence and mortality rates. The detection of tumor markers is crucial for managing cancer, making treatment decisions, and monitoring disease progression. Vascular endothelial growth factor (VEGF) and programmed death-ligand 1 (PDL-1) are key targets in cervical cancer therapy and valuable biomarkers in predicting treatment response and prognosis. In this study, we found that combining the measurement of VEGF and soluble PDL-1 can be used for diagnosing and evaluating the progression of cervical cancer. To explore a more convenient approach for detecting and assessing cervical cancer, we designed and prepared an engineered fd bacteriophage, a human-safe viral nanofiber, equipped with two peptides targeting VEGF and PD-L1. The dual-display phage nanofiber specifically recognizes and binds to both proteins. Utilizing this nanofiber as a novel capture agent, we developed a new enzyme-linked immunosorbent assay (ELISA) method. This method shows significantly enhanced detection sensitivity compared to conventional ELISA methods, which use either anti-VEGF or anti-PD-L1 antibodies as capture agents. Therefore, the phage dual-display nanofiber presents significant potential in detecting cancer markers, evaluating medication efficacy, and advancing immunotherapy drug development. Key points • The combined measurement of VEGF and soluble Programmed Death-Ligand 1(sPD-L1) demonstrates an additive effect in the diagnosis of cervical cancer. Fd phage nanofibers have been ingeniously engineered to display peptides that bind to VEGF and PD-L1, enabling the simultaneous detection of both proteins within a single assay • Genetically engineered phage nanofibers, adorned with two distinct peptides, can be utilized for the diagnosis and prognosis of cancer and can be mass-produced cost-effectively through bacterial infections • Employing dual-display fd phage nanofibers as capture probes, the phage ELISA method exhibited significantly enhanced detection sensitivity compared to traditional sandwich ELISA. Furthermore, phage ELISA facilitates the detection of a single protein or the simultaneous detection of multiple proteins, rendering them powerful tools for protein analysis and diagnosis across various fields, including cancer research Graphical Abstract

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Section: Discussionmentioning

confidence: 99%

Advanced detection of cervical cancer biomarkers using engineered filamentous phage nanofibers

Zhou,

Wang,

Bao

et al. 2024

Appl Microbiol Biotechnol

Self Cite

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“…At the same time, they have the same functions as proteins due to their similar composition [ 103 , 104 ]. In addition, phage display peptides have the advantages of high immunogenicity, high biocompatibility, high particle carrier loading rate, and can be selected as multifunctional ligands in the biomedical field, such as cell-targeting, tumor-homing, cell-penetrating [ 105 ].…”

Section: Current Engineering Strategies Based On Phagementioning

confidence: 99%

Phage-based delivery systems: engineering, applications, and challenges in nanomedicines

Wang,

Yang,

et al. 2024

J Nanobiotechnol

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Bacteriophages (phages) represent a unique category of viruses with a remarkable ability to selectively infect host bacteria, characterized by their assembly from proteins and nucleic acids. Leveraging their exceptional biological properties and modifiable characteristics, phages emerge as innovative, safe, and efficient delivery vectors. The potential drawbacks associated with conventional nanocarriers in the realms of drug and gene delivery include a lack of cell-specific targeting, cytotoxicity, and diminished in vivo transfection efficiency. In contrast, engineered phages, when employed as cargo delivery vectors, hold the promise to surmount these limitations and attain enhanced delivery efficacy. This review comprehensively outlines current strategies for the engineering of phages, delineates the principal types of phages utilized as nanocarriers in drug and gene delivery, and explores the application of phage-based delivery systems in disease therapy. Additionally, an incisive analysis is provided, critically examining the challenges confronted by phage-based delivery systems within the domain of nanotechnology. The primary objective of this article is to furnish a theoretical reference that contributes to the reasoned design and development of potent phage-based delivery systems. Graphical abstract

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“…With the development of synthetic biology and immunology, biomaterial-based adjuvants are emerging as a promising strategy to amplify antitumor immunity . M13 bacteriophages are filamentous phages consisting of a protein capsid encapsulating a single-stranded DNA. , With approximately 900 nm in length and 6 nm in width, M13 bacteriophages are characterized by the nanofiber-like morphology and have been widely studied in various fields of nanomedicine as a bionanomaterial, including tissue regeneration, biosensor, drug delivery, etc . Recent advances have focused more on the inherent immunogenicity of M13 bacteriophages.…”

Section: Introductionmentioning

confidence: 99%

Engineered Bacteriophage-Based In Situ Vaccine Remodels a Tumor Microenvironment and Elicits Potent Antitumor Immunity

Lei,

Yan,

Xin

et al. 2024

ACS Nano

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In situ vaccines (ISVs) utilize the localized delivery of chemotherapeutic agents or radiotherapy to stimulate the release of endogenous antigens from tumors, thereby eliciting systemic and persistent immune activation. Recently, a bioinspired ISV strategy has attracted tremendous attention due to its features such as an immune adjuvant effect and genetic plasticity. M13 bacteriophages are natural nanomaterials with intrinsic immunogenicity, genetic flexibility, and cost-effectiveness for large-scale production, demonstrating the potential for application in cancer vaccines. In this study, we propose an ISV based on the engineered M13 bacteriophage targeting CD40 (M13 CD40 ) for dendritic cell (DC)-targeted immune stimulation, named H-GM-M13 CD40 . We induce immunogenic cell death and release tumor antigens through local delivery of (S)-10-hydroxycamptothecin (HCPT), followed by intratumoral injection of granulocyte-macrophage colony stimulating factor (GM-CSF) and M13 CD40 to enhance DC recruitment and activation. We demonstrate that this ISV strategy can result in significant accumulation and activation of DCs at the tumor site, reversing the immunosuppressive tumor microenvironment. In addition, H-GM-M13 CD40 can synergize with the PD-1 blockade and induce abscopal effects in cold tumor models. Overall, our study verifies the immunogenicity of the engineered M13 CD40 bacteriophage and provides a proof of concept that the engineered M13 CD40 phage can function as an adjuvant for ISVs.

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Filamentous bacteriophages, natural nanoparticles, for viral vaccine strategies

Abstract: Filamentous bacteriophages are natural nanoparticles formed by the self-assembly of structural proteins that have the capability of replication and infection. They are used as a highly efficient vaccine platform to...

Cited by 7 publications

References 155 publications

Advanced detection of cervical cancer biomarkers using engineered filamentous phage nanofibers

Advanced detection of cervical cancer biomarkers using engineered filamentous phage nanofibers

Phage-based delivery systems: engineering, applications, and challenges in nanomedicines

Engineered Bacteriophage-Based In Situ Vaccine Remodels a Tumor Microenvironment and Elicits Potent Antitumor Immunity

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