Creation of Novel Nanocomplexes to Target Head and Neck Cancer

Abstract

Objective: It is critically important to develop novel targeted strategies that can efficiently inhibit specific molecular pathways in tumor growth and development. The study investigates the potential of adenoviral/chitosan-PEG nanocomplexes with epidermal growth factor (EGF) for the targeting and treatment of EGF receptor (EGFR) overexpressing head and neck cancers (HNC).

Method: A construct with GFP-expressing adenoviral vector was coated with a Chitosan-PEG-EGF nanocomplex. The EGFR-expressing HNC tumor cells labeled with TdTomato were co-cultured with CHO tumor cells with coxsackievirus and adenovirus receptor (CAR), and without EGFR. Fluorescence microscopy was used to detect GFP expression after the treatment with targeted adenoviral/chitosan nanocomplex.

Results: As compared to wild-type adenovirus, the chitosan-PEG polymer coating cloaks the viral nanoparticle and prevents interaction with cells through the native CAR-mediated mechanisms. This significantly reduces nonspecific infection. Due to the TdTomato molecular marker being specifically expressed in the EGFR tumor cell line, the treated EGFR-expressing cells can be visualized by co-registration of GFP and TdTomato. The non-EGFR-expressing cells lack TdTomato and therefore only express the GFP. The adenoviral/chitosan-PEG nanocomplexes with EGF ligand demonstrated significantly increased EGFR tumor cell-specific GFP expression. The tumor cells without EGFR showed no GFP expression.

Conclusion: Our study suggests that the novel EGFR-targeted adenoviral/chitosan-PEG nanocomplex approach can effectively target HNC and has significant potential to deliver therapeutic agents specifically to the HNC tumor sites. It is also possible to track real-time tumor growth and spread through molecular imaging by incorporating fluorescent proteins into the payload.