Amygdalin delivery via a hybrid hyaluronic acid-chitosan/carbon-metal oxide nanocomposite: In silico and in vivo anticancer evaluation in chemically induced squamous cell carcinoma mouse model.

BACKGROUND

Head and neck cutaneous squamous cell carcinoma (HNCSCC) is an aggressive metastatic neoplasm. While conventional therapies exist, they often afford suboptimal outcomes. Amygdalin (AMG) is a natural anticancer agent, but its clinical utility is hindered by cyanide toxicity, poor stability, and minimal bioavailability.

OBJECTIVE

The aim of this study was to develop a hyaluronic acid-coated, chitosan- based nanocomposite functionalized with reduced graphene oxide and zinc oxide (CS/rGO-ZnO/HA) for AMG encapsulation. The formulation's therapeutic efficacy, and systemic toxicity will be assessed in a chemically-induced cutaneous squamous cell carcinoma mouse model.

METHODS

In silico docking evaluated AMG binding affinity with NLRP3, CD44, β-catenin 1, IL-6, STAT3, and EGFR-TK. Skin cancer was induced in mice using 7,12-dimethylbenz [a]anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA), via topical application. Induced animals were subcutaneously injected with either AMG-loaded nanocomposite, free AMG, or blank nanocomposite. Anticancer efficacy was assessed by monitoring tumor volume, survival rates, and quantifying the aforementioned signaling targets. Systemic toxicity and anticancer activity were validated through histopathological analysis.

RESULTS

In silico docking analysis demonstrated robust binding affinity between AMG and the examined signaling targets. The synthesized AMG-loaded nanocomposite significantly reduced tumor volume and improved survival rates compared to all the other examined groups. Moreover, there was significant downregulation of NLRP3, CD44, β-catenin, IL-6, and STAT3. Histopathological scoring confirmed a reduction in epidermal hyperplasia, squamous cell carcinoma progression, and EGFR-TK expression, alongside reduced systemic toxicity in the major secretory organs.

CONCLUSION

Encapsulation of AMG within nanocomposites can represent a promising, multi-target strategy for treating HNCSCC.