Identification Of An Integrin Alpha 6-Targeted Peptide For Nasopharyngeal Carcinoma-Specific Nanotherapeutics

Integrin alpha 6 emerges as an attractive cancer therapeutic target. Here, the authors present for the first-time, that integrin alpha 6 is overexpressed in nasopharyngeal carcinoma (NPC) and serves as a prognostic predictor and a cancer stem cell (CSC) biomarker. An NPC-targeted peptide CRWYDENAC (dubbed RWY) with high specificity and affinity for integrin alpha 6 is identified, and an integrin alpha 6-targeted nanotherapeutic against NPC is developed by encapsulating a cisplatin prodrug Pt(IV) with RWY-grafted polymeric nanoparticles (dubbed RWY-NP/Pt(IV)). The delivery of cisplatin prodrug Pt(IV) by RWY-NP/Pt(IV) results in an approximately 100-fold increase in cytotoxicity over free cisplatin, as well as a 5-fold increase over Scramble-NP/Pt(IV) control. RWY-NP/Pt(IV) suppresses NPC tumor growth with an inhibition rate of around 78%, compared with the 44% and 41% achieved by free cisplatin and Scramble-NP/Pt(IV) treatment. Loss of body weight is observed in free cisplatin treated mice but not in RWY-NP/Pt(IV) treated mice. Taken together, RWY-NP/Pt(IV) enhances the therapeutic efficacy of cisplatin treatment and reduces deleterious side effects, suggesting the potential application of the integrin alpha 6-targeted RWY peptide for nanotherapeutics against NPC.