EGF-Liposomes Promote Efficient EGFR Targeting in Xenograft Colocarcinoma Model

Abstract

Aim: Development of EGF-liposomes (LP-EGF) for selective molecules delivery in tumors expressing EGFR. Material & methods:In vitro cellular interaction of EGF-LP and nontargeted liposomes (LP-N) was assayed at 37 and 4°C in cells expressing different EGFR levels. Receptor-mediated uptake was investigated by competition with a monoclonal antibody anti-EGFR. Selective intracellular drug delivery and efficacy was tested by oxaliplatin encapsulation. In vivo biodistribution of LP-N and LP-EGF was done in xenograft model. Results: LP-EGF was internalized by an active and selective mechanism through EGFR without receptor activation. Oxaliplatin LP-EGF decreased IC₅₀ between 48 and 13% in cell EGFR+. LP-EGF was accumulated in tumor over 72 h postdosing, while LP-N in spleen. Conclusion: LP-EGF represents an attractive nanosystem for cancer therapy or diagnosis.

Keywords:

• cetuximab
• colorectal cancer
• EGF
• EGFR
• oxaliplatin
• targeted liposomes

Acknowledgements

The authors thank the Imaging Unit from CIMA (Pamplona, Spain) the technical assistance with the microscopy assays.

Financial & competing interests disclosure

This project was funded by the Spanish Government (Instituto de Salud Carlos III, ref: PS09/02512-FISS), Government of Navarra (ref: IIQ14334.RI1), idiSNA Institute and from the University of Navarra. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.