X-ray and NIR light dual-triggered mesoporous upconversion nanophosphor/Bi heterojunction radiosensitizer for highly efficient tumor ablation

ABSTRACT Developing a multi-functional radiosensitizer with high efficiency and low toxicity remains challenging. Herein, we report a mesoporous heterostructure radiosensitizer ( [email protected] ) containing Lu-based upconversion nanophosphor (UCNP) and Bi-based nanomaterial loaded with iron phthalocyanine for X-ray and NIR light dual-triggered tri-modal tumor therapy. NaLuF 4 :Yb,Tm, a Lu-based UCNP, offers radiosensitization and upconversion luminescence for optical bio-imaging. However, Bi has a higher X-ray mass attenuation coefficient than Lu . Thus, after stepwise fabrication, Na 0.2 Bi 0.8 O 0.35 F 1.91 :Yb (NBOF) was assembled with the UCNP to form a mesoporous heterostructure composite. This enhanced the radiosensitization effect and drug load to realize multi-modal tumor therapy. After coating it with folate-conjugated amphiphilic PEG (PFA), [email protected] realized tumor photothermal/photodynamic/radio-therapy. The structure of [email protected] was well characterized. Different properties triggered by X-ray and NIR light were evaluated. Finally, a highly efficient tumor ablation effect was demonstrated in vitro and in vivo . Consequently, this kind of nanocomposite provides a unique strategy for designing a theranostic platform for oncotherapy. Statement of Significance The synergy of enhanced radiotherapy and photothermal/photodynamic therapy is found to improve tumor therapeutic efficacy. On that basis, a heterostructure nanohybrid containing Lu-based UCNP and Bi-based mesoporous material is synthesized. The heterostructure nanohybrid can be loaded with FePc and decorated with folate-modified amphiphilic PEG to form a multi-functional theranostic nano-platform. The platform exhibits upconversion luminescence capacity, X-ray attenuation property, photothermal effect, and X-ray and NIR dual-light triggered ROS generation capability. These features can not only enable upconversion luminescence/CT bioimaging of living beings but also be applied to the photothermal/photodynamic/radio- synergistic tumor ablation. To sum up, the nanomaterial offers a novel method for the construction of a new theranostic platform.