Targeting tumors with nanobodies for cancer imaging and therapy

Oliveira, Sabrina; Heukers, Raimond; Sornkom, Jirawas; Kok, Robbert J.; Henegouwen, Paul M.P. van Bergen en

doi:10.1016/j.jconrel.2013.08.298

Cited by 181 publications

(172 citation statements)

References 105 publications

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“…This means that only one immunisation is necessary for a potentially endless source of nanobodies, producing a binder that is more reliable when compared to polyclonal antibody production techniques, as well providing the potential for lower cost [16]. These benefits have enabled the development of novel [17][18][19][20], as well as showing early promise in the field of diagnostics [20,21].…”

Section: Introductionmentioning

confidence: 99%

The development and optimisation of nanobody based electrochemical immunosensors for IgG

Goode

Dillon

Millner

2016

Sensors and Actuators B: Chemical

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Article:Goode, J orcid.org/0000-0002-3642-1291, Dillon, G and Millner, PA orcid.org/0000-0002-4813-4302 (2016 ReuseUnless indicated otherwise, fulltext items are protected by copyright with all rights reserved. The copyright exception in section 29 of the Copyright, Designs and Patents Act 1988 allows the making of a single copy solely for the purpose of non-commercial research or private study within the limits of fair dealing. The publisher or other rights-holder may allow further reproduction and re-use of this version -refer to the White Rose Research Online record for this item. Where records identify the publisher as the copyright holder, users can verify any specific terms of use on the publisher's website. TakedownIf you consider content in White Rose Research Online to be in breach of UK law, please notify us by emailing eprints@whiterose.ac.uk including the URL of the record and the reason for the withdrawal request. This has led to the development of alternative immuno-reagents such as non-antibody binding proteins (NABPs). These are low molecular weight proteins which largely avoid the aforementioned advantages of antibodies. They are commonly produced by bacteria enabling the use of DNA technology to manipulate bioreceptors at the molecular level.Single chain VHHs (commonly known as nanobodies) are an antibody derived NABP adapted from camelid heavy chain antibodies which are the isolated binding domain. Whilst nanobodies have been used for diagnostic and therapeutic applications, they have limited demonstration in biosensors.In this study, both antibodies and nanobodies were used to construct a biosensor. In addition nanobody performance was optimised by introducing a novel peptide spacer. The role of nanobody orientation and spacing was thus investigated and spacer length was optimised, leading to an increase in the sensitivity of the biosensor. Highlights: Nanobodies have been used on impedimetric immunosensors to detect rabbit IgG  Unmodified nanobody sensors displayed a decrease in resistance upon analyte recognition.  Nanobodies were modified with a peptide spacer, effectively reversing this phenomena.  The use of a spacer also increased the sensitivity of the immunosensor.

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Section: Introductionmentioning

confidence: 99%

The development and optimisation of nanobody based electrochemical immunosensors for IgG

Goode

Dillon

Millner

2016

Sensors and Actuators B: Chemical

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“…[496a,503] Humanized monoclonal Abs or their production as a chimeric protein have been reported for avoiding unwanted immune responses in patients. [504] Slight improvements have also been observed through removing the Fc fragment [505] or employing antibody carbohydrates for prospering the orientation of antibodies on the surface of nanoparticles. [506] Another limitation encountered by antibodies is that they have fragile structures, which leads to rapid loss in their targeting affinity with slight alternations to their structure by environmental challenges such as temperature and enzyme.…”

Section: Antibodiesmentioning

confidence: 99%

“…[510] The Belgian company Ablynx coined the term "nanobodies" with respect to the nanometer size range of these naturally derived antigen-binding fragments, which are also termed as single domain antibodies. [511] Nanobodies, demonstrate essential characteristics such as high specificity and affinity, [504] high solubility, stability in aqueous solutions, [512] high thermal and chemical resistance, [513] capability to be chemically modified, ease of cloning, and ease of gene manipulation [496b] which relieves some restrictions related to conventional antibodies. Additionally, low immunogenicity of nanobodies which is both attributed to their high similarity with human VH sequences [514] as well as absence of Fc fragment, made nanobodies to pave their way into biomedical applications more easily.…”

Section: Antibodiesmentioning

confidence: 99%

“…Additionally, grafting nanobodies on nanoparticles have shown a considerable potential for increasing their affinity toward the target. [504] Conjugation of liposomes, [524] micelles, [525] albumin, [526] gold, [527] and magnetic [528] nanoparticles with nanobodies has been widely reported for active targeting in drug delivery applications, especially via receptormediated internalization.…”

Section: Antibodiesmentioning

confidence: 99%

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Synthesis, Functionalization, and Design of Magnetic Nanoparticles for Theranostic Applications

Mosayebi

Kiyasatfar

Laurent

2017

Adv Healthcare Materials

193

171

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In order to translate nanotechnology into medical practice, magnetic nanoparticles (MNPs) have been presented as a class of non‐invasive nanomaterials for numerous biomedical applications. In particular, MNPs have opened a door for simultaneous diagnosis and brisk treatment of diseases in the form of theranostic agents. This review highlights the recent advances in preparation and utilization of MNPs from the synthesis and functionalization steps to the final design consideration in evading the body immune system for therapeutic and diagnostic applications with addressing the most recent examples of the literature in each section. This study provides a conceptual framework of a wide range of synthetic routes classified mainly as wet chemistry, state‐of‐the‐art microfluidic reactors, and biogenic routes, along with the most popular coating materials to stabilize resultant MNPs. Additionally, key aspects of prolonging the half‐life of MNPs via overcoming the sequential biological barriers are covered through unraveling the biophysical interactions at the bio–nano interface and giving a set of criteria to efficiently modulate MNPs' physicochemical properties. Furthermore, concepts of passive and active targeting for successful cell internalization, by respectively exploiting the unique properties of cancers and novel targeting ligands are described in detail. Finally, this study extensively covers the recent developments in magnetic drug targeting and hyperthermia as therapeutic applications of MNPs. In addition, multi‐modal imaging via fusion of magnetic resonance imaging, and also innovative magnetic particle imaging with other imaging techniques for early diagnosis of diseases are extensively provided.

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“…Among these, seven products are directed to cancer, namely: rituximab (anti-CD20), bevacizumab (anti-VEGF), alemtuzumab (anti-CD52) and targeted to EGFR: cetuximab, penitumumab, trastuzumab (anti-HER2), and matuzumab. [159][160][161] Therapeutic antibodies provide clinical benefit to patients with cancer and have been established as "standard of care" agents for several highly prevalent human cancers.…”

Section: Conclusion: Hopes and Challengesmentioning

confidence: 99%

Toward a magic or imaginary bullet? Ligands for drug targeting to cancer cells: principles, hopes, and challenges

Toporkiewicz¹,

Meissner²,

Matusewicz³

et al. 2015

IJN

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There are many problems directly correlated with the systemic administration of drugs and how they reach their target site. Targeting promises to be a hopeful strategy as an improved means of drug delivery, with reduced toxicity and minimal adverse side effects. Targeting exploits the high affinity of cell-surface-targeted ligands, either directly or as carriers for a drug, for specific retention and uptake by the targeted diseased cells. One of the most important parameters which should be taken into consideration in the selection of an appropriate ligand for targeting is the binding affinity ( K D ). In this review we focus on the importance of binding affinities of monoclonal antibodies, antibody derivatives, peptides, aptamers, DARPins, and small targeting molecules in the process of selection of the most suitable ligand for targeting of nanoparticles. In order to provide a critical comparison between these various options, we have also assessed each technology format across a range of parameters such as molecular size, immunogenicity, costs of production, clinical profiles, and examples of the level of selectivity and toxicity of each. Wherever possible, we have also assessed how incorporating such a targeted approach compares with, or is superior to, original treatments.

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Targeting tumors with nanobodies for cancer imaging and therapy

Cited by 181 publications

References 105 publications

The development and optimisation of nanobody based electrochemical immunosensors for IgG

The development and optimisation of nanobody based electrochemical immunosensors for IgG

Synthesis, Functionalization, and Design of Magnetic Nanoparticles for Theranostic Applications

Toward a magic or imaginary bullet? Ligands for drug targeting to cancer cells: principles, hopes, and challenges

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