Ordered arrangement of hydrated GdPO4 nanorods in magnetic chitosan matrix promotes tumor photothermal therapy and bone regeneration against breast cancer bone metastases

Abstract

Surgical resection is a traditionally therapeutic strategy against breast cancer-induced bone metastases; however, it may cause cancer recurrence and local bone defects. Herein, Fe3O4 nanoparticles and hydrated GdPO4 nanorods were incorporated in bioactive chitosan (CS) matrix, forming multifunctional GdPO4/CS/Fe3O4 scaffolds for tumor photothermal therapy and bone tissue regeneration. The Fe3O4 nanoparticles in the GdPO4/CS/Fe3O4 scaffolds improved near-infrared (NIR) absorption capacity and photothermal conversion efficiency. Under the NIR laser irradiation, the local temperatures around the GdPO4/CS/Fe3O4 scaffolds were elevated high enough to stimulate the apoptosis of tumor cells, effectively avoiding postoperative cancer recurrence. The hydrated GdPO4 nanorods served as a novel bioactive component for enhanced angiogenesis and osteogenesis abilities. The as-released Gd3+ ions from the GdPO4/CS/Fe3O4 scaffolds induced the M2 polarization of macrophages for stabilizing as-formed vasculature. The newly formed blood vessels provided oxygen and nutrient for osteogenesis. Moreover, the hydrated GdPO4 nanorods in the scaffolds activated BMP-2/Smad/RUNX2 signaling pathway that facilitated cell proliferation, differentiation and bone tissue regeneration. Hence, the multifunctional GdPO4/CS/Fe3O4 scaffolds enable the photothermal ablation of postoperative residual tumors and subsequent bone defect healing, which may become a promising platform for the therapy of breast cancer bone metastases.