Self-Assembling VHH-Elastin-Like Peptides for Photodynamic Nanomedicine
Publication year
2017Source
Biomacromolecules, 18, 4, (2017), pp. 1302-1310ISSN
Publication type
Article / Letter to editor
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Organization
Bio-organic Chemistry
Pathology
Radboud Institute for Molecular Life Sciences
Journal title
Biomacromolecules
Volume
vol. 18
Issue
iss. 4
Page start
p. 1302
Page end
p. 1310
Subject
Bio-Organic Chemistry; Radboudumc 19: Nanomedicine RIMLS: Radboud Institute for Molecular Life Sciences; Pathology Radboud University Medical CenterAbstract
Recombinant llama heavy-chain antibody fragments (VHHs) are promising tools in the field of targeted nanomedicine. 7D12, a VHH against the epidermal growth factor receptor (EGFR) that is overexpressed in various cancers, has been evaluated as an effective cancer-targeting VHH in multiple studies. The small size of VHHs (15-20 kDa) results in a low circulation half-life, which can be disadvantageous for certain applications. A solution to this problem is to attach VHHs to the surface of nanoparticles to increase the hydrodynamic radius of the conjugate. This approach simultaneously allows the incorporation of different VHHs and other targeting moieties and therapeutic components into one structure, creating multispecificity and versatility for therapy and diagnosis. Here, we present the construction of highly defined 7D12-containing nanoparticles by utilizing thermoresponsive diblock elastin-like peptides that reversibly self-assemble into micellar structures. The resulting particles have a hydrodynamic radius of 24.3 +/- 0.9 nm and retain full EGFR-binding capacity. We present proof of concept of the usability of such particles by controlled incorporation of a photosensitizer and show that the resulting nanoparticles induce EGFR-specific light-induced cell killing. This approach is easily extended to the controlled incorporation of various functional modules, improving therapy and diagnosis with targeted nanomedicine.
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