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

Jie Liu; Jing Zhang; Fei Huang; Yong Deng; Bing Li; Ruizhuo Ouyang; Yuqing Miao; Yun Sun; Yuhao Li

doi:10.1016/j.actbio.2020.06.044

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

Acta Biomater. 2020 Sep 1:113:570-583. doi: 10.1016/j.actbio.2020.06.044. Epub 2020 Jul 3.

Authors

Jie Liu¹, Jing Zhang¹, Fei Huang¹, Yong Deng¹, Bing Li², Ruizhuo Ouyang¹, Yuqing Miao¹, Yun Sun³, Yuhao Li⁴

Affiliations

¹ Institute of Bismuth Science, College of Science, University of Shanghai for Science and Technology, Shanghai 200093, China.
² Department of Research and Development & Department of Nuclear Medicine, Shanghai Proton and Heavy Ion Center, Fudan University Shanghai Cancer Center, Shanghai 201321, China; Shanghai Engineering Research Center of Proton and Heavy Ion Radiation Therapy, Shanghai 201321, China.
³ Department of Research and Development & Department of Nuclear Medicine, Shanghai Proton and Heavy Ion Center, Fudan University Shanghai Cancer Center, Shanghai 201321, China; Shanghai Engineering Research Center of Proton and Heavy Ion Radiation Therapy, Shanghai 201321, China. Electronic address: yun.sun@sphic.org.cn.
⁴ Institute of Bismuth Science, College of Science, University of Shanghai for Science and Technology, Shanghai 200093, China. Electronic address: yhli@usst.edu.cn.

PMID: 32629190
DOI: 10.1016/j.actbio.2020.06.044

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. NaLuF₄: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_0.2Bi_0.8O_0.35F_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), 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.

Keywords: Bi; Heterojunction structure; Theranostic; Upconversion nanophosphor.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Humans
Nanoparticles*
Neoplasms*
Phototherapy
Radiation-Sensitizing Agents* / pharmacology
X-Rays

Substances

Radiation-Sensitizing Agents