Phage-based Delivery Systems: Engineering, Applications, and Challenges in Nanomedicines

Overview

Journal J Nanobiotechnology

Publisher Biomed Central

Specialty Biotechnology

Date 2024 Jun 25

PMID 38918839

Authors

Hui Wang

Ying Yang

Yan Xu

Yi Chen

Wenjie Zhang

Tianqing Liu

Gang Chen

Kaikai Wang

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Whole-body Bacteriophage Distribution Characterized by a Physiologically based Pharmacokinetic Model.

Echterhof A, Dharmaraj T, Blankenberg P, Targ B, Bollyky P, Smith N bioRxiv. 2025; .

PMID: 39975270 PMC: 11839030. DOI: 10.1101/2025.02.06.636931.

Developing a Versatile Arsenal: Novel Antimicrobials as Offensive Tools Against Pathogenic Bacteria.

Ma J, Lu Z Microorganisms. 2025; 13(1).

PMID: 39858940 PMC: 11767912. DOI: 10.3390/microorganisms13010172.

Engineered Phage Enables Efficient Control of Gene Expression upon Infection of the Host Cell.

Wei T, Lai W, Chen Q, Sun C Int J Mol Sci. 2025; 26(1.

PMID: 39796105 PMC: 11720261. DOI: 10.3390/ijms26010250.

A Critical Analysis of the Opportunities and Challenges of Phage Application in Seafood Quality Control.

Yan J, Guo Z, Xie J Foods. 2024; 13(20).

PMID: 39456344 PMC: 11506950. DOI: 10.3390/foods13203282.

A Comprehensive Review on Phage Therapy and Phage-Based Drug Development.

Cui L, Watanabe S, Miyanaga K, Kiga K, Sasahara T, Aiba Y Antibiotics (Basel). 2024; 13(9).

PMID: 39335043 PMC: 11428490. DOI: 10.3390/antibiotics13090870.

References

Kehoe J, Kay B . Filamentous phage display in the new millennium. Chem Rev. 2005; 105(11):4056-72. DOI: 10.1021/cr000261r. View

Chang C, Guo W, Yu X, Guo C, Zhou N, Guo X . Engineered M13 phage as a novel therapeutic bionanomaterial for clinical applications: From tissue regeneration to cancer therapy. Mater Today Bio. 2023; 20:100612. PMC: 10102448. DOI: 10.1016/j.mtbio.2023.100612. View

Heinis C, Rutherford T, Freund S, Winter G . Phage-encoded combinatorial chemical libraries based on bicyclic peptides. Nat Chem Biol. 2009; 5(7):502-7. DOI: 10.1038/nchembio.184. View

Yata T, Lee K, Dharakul T, Songsivilai S, Bismarck A, Mintz P . Hybrid Nanomaterial Complexes for Advanced Phage-guided Gene Delivery. Mol Ther Nucleic Acids. 2014; 3:e185. PMC: 4221597. DOI: 10.1038/mtna.2014.37. View

Lockett M, Phillips M, Jarecki J, Peelen D, Smith L . A tetrafluorophenyl activated ester self-assembled monolayer for the immobilization of amine-modified oligonucleotides. Langmuir. 2007; 24(1):69-75. PMC: 2533856. DOI: 10.1021/la702493u. View

Chen G, Ullah A, Xu G, Xu Z, Wang F, Liu T . Topically applied liposome-in-hydrogels for systematically targeted tumor photothermal therapy. Drug Deliv. 2021; 28(1):1923-1931. PMC: 8462874. DOI: 10.1080/10717544.2021.1974607. View

Zhu J, Batra H, Ananthaswamy N, Mahalingam M, Tao P, Wu X . Design of bacteriophage T4-based artificial viral vectors for human genome remodeling. Nat Commun. 2023; 14(1):2928. PMC: 10229621. DOI: 10.1038/s41467-023-38364-1. View

Zhu J, Tao P, Mahalingam M, Sha J, Kilgore P, Chopra A . A prokaryotic-eukaryotic hybrid viral vector for delivery of large cargos of genes and proteins into human cells. Sci Adv. 2019; 5(8):eaax0064. PMC: 6703872. DOI: 10.1126/sciadv.aax0064. View

Galaway F, Stockley P . MS2 viruslike particles: a robust, semisynthetic targeted drug delivery platform. Mol Pharm. 2012; 10(1):59-68. DOI: 10.1021/mp3003368. View

10.

Hsu B, Way J, Silver P . Stable Neutralization of a Virulence Factor in Bacteria Using Temperate Phage in the Mammalian Gut. mSystems. 2020; 5(1). PMC: 6989128. DOI: 10.1128/mSystems.00013-20. View

11.

Pugazhendhi A, Edison T, Karuppusamy I, Kathirvel B . Inorganic nanoparticles: A potential cancer therapy for human welfare. Int J Pharm. 2018; 539(1-2):104-111. DOI: 10.1016/j.ijpharm.2018.01.034. View

12.

Wang F, Liu P, Sun L, Li C, Petrenko V, Liu A . Bio-mimetic nanostructure self-assembled from Au@Ag heterogeneous nanorods and phage fusion proteins for targeted tumor optical detection and photothermal therapy. Sci Rep. 2014; 4:6808. PMC: 4210868. DOI: 10.1038/srep06808. View

13.

Petrov G, Dymova M, Richter V . Bacteriophage-Mediated Cancer Gene Therapy. Int J Mol Sci. 2022; 23(22). PMC: 9697857. DOI: 10.3390/ijms232214245. View

14.

Ullah A, Wang K, Wu P, Oupicky D, Sun M . CXCR4-targeted liposomal mediated co-delivery of pirfenidone and AMD3100 for the treatment of TGFβ-induced HSC-T6 cells activation. Int J Nanomedicine. 2019; 14:2927-2944. PMC: 6501422. DOI: 10.2147/IJN.S171280. View

15.

Lankes H, Zanghi C, Santos K, Capella C, Duke C, Dewhurst S . In vivo gene delivery and expression by bacteriophage lambda vectors. J Appl Microbiol. 2007; 102(5):1337-49. PMC: 2063594. DOI: 10.1111/j.1365-2672.2006.03182.x. View

16.

Nicastro J, Sheldon K, Slavcev R . Bacteriophage lambda display systems: developments and applications. Appl Microbiol Biotechnol. 2014; 98(7):2853-66. DOI: 10.1007/s00253-014-5521-1. View

17.

Peng H, Rossetto D, Mansy S, Jordan M, Roos K, Chen I . Treatment of Wound Infections in a Mouse Model Using Zn-Releasing Phage Bound to Gold Nanorods. ACS Nano. 2022; 16(3):4756-4774. PMC: 8981316. DOI: 10.1021/acsnano.2c00048. View

18.

Hashemi H, Bamdad T, Jamali A, Pouyanfard S, Mohammadi M . Evaluation of humoral and cellular immune responses against HSV-1 using genetic immunization by filamentous phage particles: a comparative approach to conventional DNA vaccine. J Virol Methods. 2009; 163(2):440-4. DOI: 10.1016/j.jviromet.2009.11.008. View

19.

Lehti T, Pajunen M, Skog M, Finne J . Internalization of a polysialic acid-binding Escherichia coli bacteriophage into eukaryotic neuroblastoma cells. Nat Commun. 2017; 8(1):1915. PMC: 5715158. DOI: 10.1038/s41467-017-02057-3. View

20.

Bazan J, Calkosinski I, Gamian A . Phage display--a powerful technique for immunotherapy: 1. Introduction and potential of therapeutic applications. Hum Vaccin Immunother. 2012; 8(12):1817-28. PMC: 3656071. DOI: 10.4161/hv.21703. View