Transferrin-Mediated Targeting of Bacteriophage HK97 Nanoparticles Into Tumor Cells

Huang, Rick; Steinmetz, Nicole F.; Fu, Chiyu; Manchester, Marianne; Johnson, John E.

doi:10.2217/nnm.10.99

Cited by 56 publications

(52 citation statements)

References 59 publications

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“…A distinct advantage of bacteriophage HK97 is that, due to the different maturation states of the bacteriophage capsid head, a range of HK97 particles with different sizes, internal capacity, stability and dynamics could be explored for cell uptake studies. Confocal imaging confirmed that the functionalized HK97 particles were internalized in cancer cells via endocytosis in clathrin-coated pits, which were subsequently targeted and localized to the endolysosomal compartment (Huang et al, 2011).…”

Section: Molecular Detectionmentioning

confidence: 83%

Using viruses as nanomedicines

Kan-Davelaar

Hest

Cornelissen

et al. 2014

British J Pharmacology

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The field of nanomedicine involves the design and fabrication of novel nanocarriers for the intracellular delivery of therapeutic cargo or for use in molecular diagnostics. Although traditionally recognized for their ability to invade and infect host cells, viruses and bacteriophages have been engineered over the past decade as highly promising molecular platforms for the targeted delivery and treatment of many human diseases. Inherently biodegradable, the outer capsids of viruses are composed entirely of protein building blocks, which can be genetically or chemically engineered with molecular imaging reagents, targeting ligands and therapeutic molecules. While there are several examples of viruses as in vitro molecular cargo carriers, their potential for applications in nanomedicine has only recently emerged. Here we highlight recent developments towards the design and engineering of viruses for the treatment of cancer, bacterial infections and immune system-related diseases. LINKED ARTICLESThis article is part of a themed section on Nanomedicine. To view the other articles in this section visit http://dx

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Section: Molecular Detectionmentioning

confidence: 83%

Using viruses as nanomedicines

Kan-Davelaar

Hest

Cornelissen

et al. 2014

British J Pharmacology

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“…151 CPMV displaying peptide F56, which was discovered through phage display, has been used to target vascular endothelial growth fa ctor receptor-1 (VEGFR-1), with accumulation throughout the tumor observed compared to no detectable uptake of non-targeted particles. 99 Other options that have been explored include FR targeting with folic acid (FA), 164, 184, 185 TfR with transferrin, 186 and prostate specific membrane antigen (PSMA) with a PSMA antibody. 187 In recent years, a target that has been approached from many angles is epidermal growth factor receptor (EGFR), an important biomarker overexpressed on many malignant cell types.…”

Section: Applications Of Virus-based Particlesmentioning

confidence: 99%

Design of virus-based nanomaterials for medicine, biotechnology, and energy

2016

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Virus-based nanomaterials are versatile materials that naturally self-assemble and have relevance for a broad range of applications including medicine, biotechnology, and energy. This review provides an overview of recent developments in “chemical virology.” Viruses, as materials, provide unique nanoscale scaffolds that have relevance in chemical biology and nanotechnology, with diverse areas of applications. Some fundamental advantages of viruses, compared to synthetically programmed materials, include the highly precise spatial arrangement of their subunits into a diverse array of shapes and sizes and many available avenues for easy and reproducible modification. Here, we will first survey the broad distribution of viruses and various methods for producing virus-based nanoparticles, as well as engineering principles used to impart new functionalities. We will then examine the broad range of applications and implications of virus-based materials, focusing on the medical, biotechnology, and energy sectors. We anticipate that this field will continue to evolve and grow, with exciting new possibilities stemming from advancements in the rational design of virus-based nanomaterials.

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“…The HK97 fold has been detected in every tailed phage capsid that has been imaged at sufficient resolution, including P22 11; 12; 13 , T4 14 , λ 15 , ϕ29 16 , T5 17; 18 , P2/P4 19 , epsilon15 20 , T7 21; 22 , the tailed-phage-like archaevirus HSTV-1 23 , in the base layer of the Herpesvirus (HSV1) major capsid protein 24 and in the bacterial comparments known as encapsulins 25 . With renewed interest in phage therapy to combat multiple-drug-resistant bacterial pathogens 26; 27; 28 , and an emerging interest in using bacteriophage capsids as platforms for nanotechnology 29 (http://www.nano.gov/) directed to the treatment of disease 30; 31 and the creation of new technologies 32; 33; 34; 35 , it is important to have a deep understanding of capsid structures and assembly pathways in order that they can be manipulated and utilized to the greatest extent.…”

Section: Introductionmentioning

confidence: 99%

Transient Contacts on the Exterior of the HK97 Procapsid That Are Essential for Capsid Assembly

Tso¹,

Hendrix²,

Duda³

2014

Journal of Molecular Biology

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The G-loop is a 10-residue glycine-rich loop that protrudes from the surface of the mature bacteriophage HK97 capsid at the C-terminal end of the long backbone helix of major capsid protein subunits. The G-loop is essential for assembly, is conserved in related capsid and encapsulin proteins, and plays its role during HK97 capsid assembly by making crucial contacts between the hill-like hexamers and pentamers in precursor proheads. These contacts are not preserved in the flattened capsomers of the mature capsid. Aspartate 231 in each of the ~400 G-loops interacts with Lysine 178 of the E-loop (Extended Loop) of a subunit on an adjacent capsomer. Mutations disrupting this interaction prevented correct assembly, and in some cases induced abnormal assembly into tubes, or small, incomplete capsids. Assembly remained defective when D231 and K178 were replaced with larger charged residues or when their positions were exchanged. Second-site suppressors of lethal mutants containing substitution D231L replaced the ionic interaction with new interactions between neutral or hydrophobic residues of about the same size: D231L/K178V, D231L/K178I, and D231L/K178N. We conclude that it is not the charge, but the size and shape of the side chains of residues 178 and 231 that are important. These two residues control the geometry of contacts between the E-loop and the G-loop, which apparently must be precisely spaced and oriented for correct assembly to occur. We present a model for how the G-loop could control HK97 assembly and identify G-loop-like protrusions in other capsid proteins that may play analogous roles.

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Transferrin-Mediated Targeting of Bacteriophage HK97 Nanoparticles Into Tumor Cells

Cited by 56 publications

References 59 publications

Using viruses as nanomedicines

Using viruses as nanomedicines

Design of virus-based nanomaterials for medicine, biotechnology, and energy

Transient Contacts on the Exterior of the HK97 Procapsid That Are Essential for Capsid Assembly

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