Enhanced radiosensitivity and chemoradiation efficacy in nasopharyngeal carcinoma via a dual-targeted SPION@polymer hybrid nanosensitizer

Cisplatin-based nanoparticles show good potential in enhancing the effect of nasopharynx carcinoma (NPC) therapy but are still limited by their low radiation sensitization and poor tumor targeting ability. Herein, an ingenious design of multifunctional superparamagnetic iron oxide nanoparticle (SPION)@polymer hybrid nanosensitizer (SPHN) with enhanced radiosensitization and dual-targeting capability is described. SPHN have a core-shell structure, in which radiosensitizer superparamagnetic iron oxide particle (SPION) and cis-platinum (CDDP) are encapsulated in RGD-conjugated amphiphilic block copolymers. These unique structures endow SPHN with outstanding radiosensitization and tumor targeting abilities. When combined with X-rays, SPHN showed strong promotion of the apoptosis of CNE-1 cells in vitro. In addition, RNA-seq and KEGG enrichment analyses indicated that the PI3K-Akt and TNF signaling pathways were closely related to the molecular mechanism of SPHN in chemoradiotherapy. Furthermore, gene set enrichment analysis (GSEA) revealed that SPHN + X-rays treatment decreased translation initiation pathways and the cytoplasmic translation pathway. Through a combination of radiation and chemotherapy, SPHN can achieve remarkable inhibition of tumor growth in vivo, making this nanotechnology a general platform for the chemoradiation therapy of NPC in the future. SPHNs can effectively accumulate in solid tumor via magnetic-RGD dual-targeting effect for valid CDDP delivery, resulting in a significantly improved antitumor effect with minimal side effects.