title: Hybrid Nanomaterial Complexes for Advanced Phage-guided Gene Delivery.
abstract: Developing nanomaterials that are effective, safe, and selective for gene transfer applications is challenging. Bacteriophages (phage), viruses that infect bacteria only, have shown promise for targeted gene transfer applications. Unfortunately, limited progress has been achieved in improving their potential to overcome mammalian cellular barriers. We hypothesized that chemical modification of the bacteriophage capsid could be applied to improve targeted gene delivery by phage vectors into mammalian cells. Here, we introduce a novel hybrid system consisting of two classes of nanomaterial systems, cationic polymers and M13 bacteriophage virus particles genetically engineered to display a tumor-targeting ligand and carry a transgene cassette. We demonstrate that the phage complex with cationic polymers generates positively charged phage and large aggregates that show enhanced cell surface attachment, buffering capacity, and improved transgene expression while retaining cell type specificity. Moreover, phage/polymer complexes carrying a therapeutic gene achieve greater cancer cell killing than phage alone. This new class of hybrid nanomaterial platform can advance targeted gene delivery applications by bacteriophage.
authors.affiliation: Phage Therapy Group, Department of Medicine, Imperial College London, London, UK.
authors.forename: Teerapong
authors.initials: T
authors.lastname: Yata
authors.affiliation: Polymers and Composites Engineering (PaCE) Group, Department of Chemical Engineering, Imperial College London, London, UK.
authors.forename: Koon-Yang
authors.initials: KY
authors.lastname: Lee
authors.affiliation: National Nanotechnology Center, National Science and Technology Development Agency, Khlong Luang Pathumthani, Thailand.
authors.forename: Tararaj
authors.initials: T
authors.lastname: Dharakul
authors.affiliation: National Nanotechnology Center, National Science and Technology Development Agency, Khlong Luang Pathumthani, Thailand.
authors.forename: Sirirurg
authors.initials: S
authors.lastname: Songsivilai
authors.affiliation: Polymers and Composites Engineering (PaCE) Group, Department of Chemical Engineering, Imperial College London, London, UK.
authors.forename: Alexander
authors.initials: A
authors.lastname: Bismarck
authors.affiliation: Department of Surgery and Cancer, Imperial College London, London, UK.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Mintz
authors.affiliation: Phage Therapy Group, Department of Medicine, Imperial College London, London, UK.
authors.forename: Amin
authors.initials: A
authors.lastname: Hajitou