Improvement and extension of anti-EGFR targeting in breast cancer therapy by integration with the Avidin-Nucleic-Acid-Nano-Assemblies.
Francesco RoncatoFatlum RrugaElena PorcùElisabetta CasarinRoberto RoncaFederica MaccarinelliNicola RealdonGiuseppe BassoRonen AlonGiampietro ViolaMargherita MorpurgoPublished in: Nature communications (2018)
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.
Keyphrases
- nucleic acid
- cancer therapy
- small cell lung cancer
- wild type
- poor prognosis
- epidermal growth factor receptor
- tyrosine kinase
- metastatic colorectal cancer
- diffusion weighted imaging
- drug delivery
- diffusion weighted
- locally advanced
- long non coding rna
- magnetic resonance imaging
- contrast enhanced
- stem cells
- squamous cell carcinoma
- emergency department
- radiation therapy
- mass spectrometry
- adverse drug
- drug induced
- mesenchymal stem cells
- case control