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

Liu, Jie; Zhang, Jing; Huang, Fei; Deng, Yong; Li, Bing; Ouyang, Ruizhuo; Miao, Yuqing; Sun, Yun et al. · Acta Biomater · 2020

basic_science · Level V

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Abstract

Developing a multi-functional radiosensitizer with high efficiency and low toxicity remains challenging. Herein, we report a mesoporous heterostructure radiosensitizer (UCNP@NBOF-FePc-PFA) 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<sub>4</sub>: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<sub>0.2</sub>Bi<sub>0.8</sub>O<sub>0.35</sub>F<sub>1.91</sub>: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), UCNP@NBOF-FePc-PFA realized tumor photothermal/photodynamic/radio-therapy. The structure of UCNP@NBOF-FePc-PFA 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.

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