Tumour homing and therapeutic effect of colloidal nanoparticles depend on the number of attached antibodies

Miriam Colombo, Luisa Fiandra, Giulia Alessio, Serena Mazzucchelli, Manuela Nebuloni, Clara De Palma, Karsten Kantner, Beatriz Pelaz, Rany Rotem, Fabio Corsi, Wolfgang J. Parak () and Davide Prosperi ()
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Miriam Colombo: Università di Milano-Bicocca
Luisa Fiandra: Ospedale L. Sacco
Giulia Alessio: Università di Milano-Bicocca
Serena Mazzucchelli: Ospedale L. Sacco
Manuela Nebuloni: Ospedale L. Sacco
Clara De Palma: Ospedale L. Sacco
Karsten Kantner: Fachbereich Physik, Philipps Universität Marburg
Beatriz Pelaz: Fachbereich Physik, Philipps Universität Marburg
Rany Rotem: Università di Milano-Bicocca
Fabio Corsi: Università di Milano
Wolfgang J. Parak: Fachbereich Physik, Philipps Universität Marburg
Davide Prosperi: Università di Milano-Bicocca

Nature Communications, 2016, vol. 7, issue 1, 1-14

Abstract: Abstract Active targeting of nanoparticles to tumours can be achieved by conjugation with specific antibodies. Specific active targeting of the HER2 receptor is demonstrated in vitro and in vivo with a subcutaneous MCF-7 breast cancer mouse model with trastuzumab-functionalized gold nanoparticles. The number of attached antibodies per nanoparticle was precisely controlled in a way that each nanoparticle was conjugated with either exactly one or exactly two antibodies. As expected, in vitro we found a moderate increase in targeting efficiency of nanoparticles with two instead of just one antibody attached per nanoparticle. However, the in vivo data demonstrate that best effect is obtained for nanoparticles with only exactly one antibody. There is indication that this is based on a size-related effect. These results highlight the importance of precisely controlling the ligand density on the nanoparticle surface for optimizing active targeting, and that less antibodies can exhibit more effect.

Date: 2016
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DOI: 10.1038/ncomms13818

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