Physicochemical Tools: Toward a Detailed Understanding of the Architecture of Targeted Radiotherapy Nanoparticles

Gema Cabello (Corresponding Author), Kenneth C. Nwoko, Marco Mingarelli, Abbie C. McLaughlin, Laurent Trembleau, Joerg Feldmann, Angel Cuesta Ciscar, Tim A. D. Smith

Research output: Contribution to journalArticle

Abstract

Targeted radiotherapy is proving to be an effective alternative to external beam radiotherapy for cancer treatment. Gold nanoparticles are biocompatible, commercially available, and readily functionalized, which makes them perfect candidates for the delivery of cytotoxic radionuclides labeled with antibodies to proteins abnormally expressed on cancer tissue. However, there is a lack of information regarding the efficacy of the successive modification steps involved in the functionalization process, as well as of the actual final state of the nanoparticles prior to preclinical tests, which results in a very inefficient screening and that will further impact on biological barriers, such as half-life interactions with serum proteins. Here, gold nanoparticles (15 nm diameter) were functionalized with linkers for antibody and radionuclide conjugation, following a well-stablished method. Successful coating of the gold nanoparticles was demonstrated using state-of-the-art physicochemical techniques, which include AF4-UV-ICPMS-MALS, Raman spectroscopy, and force–distance spectroscopy, which have led to an accurate description of the hydrodynamic diameter of the functionalized NPs and also about the adhesion energy and elastic properties of the modified NPs. Successive steps involved in the coating led to an organic shell of 12 nm diameter and no nanoparticle aggregation was observed. This may be a consequence of a decrease (or even the total absence) in water adsorption on the metal surface and/or of the organic labeling, that decreases the surface tension of the particles as estimated from the atomic force microscopy force–distance curves. Radiolabeling of gold nanoparticles prescreened using these physicochemical tools with 177Lu resulted in >75% efficiency.
Original languageEnglish
Pages (from-to)1639-1646
Number of pages8
JournalACS Applied Bio Materials
Volume1
Issue number5
Early online date19 Oct 2018
DOIs
Publication statusPublished - 2018

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Radiotherapy
Nanoparticles
Gold
Radioisotopes
Coatings
Oncology
Antibodies
Labeling
Surface tension
Raman spectroscopy
Blood Proteins
Atomic force microscopy
Screening
Adhesion
Agglomeration
Hydrodynamics
Metals
Spectroscopy
Tissue
Adsorption

Keywords

  • targeted radiotherapy
  • radionuclide carriers
  • force−distance spectroscopy
  • asymmetric flow field-flow fractionation
  • nanoparticle adhesion energy

Cite this

Physicochemical Tools : Toward a Detailed Understanding of the Architecture of Targeted Radiotherapy Nanoparticles. / Cabello, Gema (Corresponding Author); Nwoko, Kenneth C.; Mingarelli, Marco; McLaughlin, Abbie C.; Trembleau, Laurent; Feldmann, Joerg; Cuesta Ciscar, Angel; Smith, Tim A. D.

In: ACS Applied Bio Materials, Vol. 1, No. 5, 2018, p. 1639-1646.

Research output: Contribution to journalArticle

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