Improvement and extension of anti-EGFR targeting in breast cancer therapy by integration with the Avidin-Nucleic-Acid-Nano-Assemblies

Francesco Roncato, Fatlum Rruga, Elena Porcù, Elisabetta Casarin, Roberto Ronca, Federica Maccarinelli, Nicola Realdon, Giuseppe Basso, Ronen Alon, Giampietro Viola and Margherita Morpurgo ()
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Francesco Roncato: Università di Padova
Fatlum Rruga: Università di Padova
Elena Porcù: Università di Padova
Elisabetta Casarin: ANANAS nanotech, S.r.l.
Roberto Ronca: University of Brescia
Federica Maccarinelli: University of Brescia
Nicola Realdon: Università di Padova
Giuseppe Basso: Università di Padova
Ronen Alon: The Weizmann Institute of Science
Giampietro Viola: Università di Padova
Margherita Morpurgo: Università di Padova

Nature Communications, 2018, vol. 9, issue 1, 1-11

Abstract: Abstract Nowadays, personalized cancer therapy relies on small molecules, monoclonal antibodies, or antibody–drug conjugates (ADC). Many nanoparticle (NP)-based drug delivery systems are also actively investigated, but their advantage over ADCs has not been demonstrated yet. Here, using the Avidin-Nucleic-Acid-Nano-Assemblies (ANANAS), a class of polyavidins multifuctionalizable with stoichiometric control, we compare quantitatively anti-EGFR antibody(cetuximab)-targeted NPs to the corresponding ADC. We show that ANANAS tethering of cetuximab promotes a more efficient EGFR-dependent vesicle-mediated internalization. Cetuximab-guided ANANAS carrying doxorubicin are more cytotoxic in vitro and much more potent in vivo than the corresponding ADC, leading to 43% tumor reduction at low drug dosage (0.56 mg/kg). Advantage of cetuximab-guided ANANAS with respect to the ADC goes beyond the increase in drug-to-antibody ratio. Even if further studies are needed, we propose that NP tethering could expand application of the anti-EGFR antibody to a wider number of cancer patients including the KRAS-mutated ones, currently suffering from poor prognosis.

Date: 2018
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DOI: 10.1038/s41467-018-06602-6

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