Inhibiting tumor oxygen metabolism and simultaneously generating oxygen by intelligent upconversion nanotherapeutics for enhanced photodynamic therapy

Dan Wang; Bin Xue; Tymish Y Ohulchanskyy; Yubin Liu; Artem Yakovliev; Roman Ziniuk; Mengze Xu; Jun Song; Junle Qu; Zhen Yuan

doi:10.1016/j.biomaterials.2020.120088

Inhibiting tumor oxygen metabolism and simultaneously generating oxygen by intelligent upconversion nanotherapeutics for enhanced photodynamic therapy

Biomaterials. 2020 May 3:251:120088. doi: 10.1016/j.biomaterials.2020.120088. Online ahead of print.

Authors

Dan Wang¹, Bin Xue², Tymish Y Ohulchanskyy³, Yubin Liu⁴, Artem Yakovliev³, Roman Ziniuk³, Mengze Xu⁴, Jun Song⁵, Junle Qu⁶, Zhen Yuan⁷

Affiliations

¹ Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Physics and Optoelectronic Engineering, Shenzhen University, Shenzhen, 518060, China; College of Information Engineering, Shenzhen University, Shenzhen, 518060, China; Cancer Centre, Faculty of Health Sciences, University of Macau, Macao, China; Centre for Cognitive and Brain Sciences, University of Macau, Macao, China.
² Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Physics and Optoelectronic Engineering, Shenzhen University, Shenzhen, 518060, China; Cancer Centre, Faculty of Health Sciences, University of Macau, Macao, China; Centre for Cognitive and Brain Sciences, University of Macau, Macao, China.
³ Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Physics and Optoelectronic Engineering, Shenzhen University, Shenzhen, 518060, China.
⁴ Cancer Centre, Faculty of Health Sciences, University of Macau, Macao, China; Centre for Cognitive and Brain Sciences, University of Macau, Macao, China.
⁵ Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Physics and Optoelectronic Engineering, Shenzhen University, Shenzhen, 518060, China. Electronic address: [email protected].
⁶ Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Physics and Optoelectronic Engineering, Shenzhen University, Shenzhen, 518060, China. Electronic address: [email protected].
⁷ Cancer Centre, Faculty of Health Sciences, University of Macau, Macao, China; Centre for Cognitive and Brain Sciences, University of Macau, Macao, China. Electronic address: [email protected].

PMID: 32388167
DOI: 10.1016/j.biomaterials.2020.120088

Abstract

Hypoxia is one of the hallmarks of solid tumor, which heavily restricts the clinical cancer therapy treatments, especially for the oxygen (O₂) -dependent photodynamic therapy (PDT). Herein, an intelligent multi-layer nanostructure was developed for decreasing the O₂-consumption and elevating the O₂-supply simultaneously. The cell respiration inhibitor -atovaquone (ATO) molecules were reserved in the middle mesoporous silicon layer, and thus were intelligently released at the tumor site after the degradation of gatekeeper of MnO₂ layer, which effectively inhibit tumor respiration metabolism to elevate oxygen content. Meanwhile, the degradation of MnO₂ layer can generate O₂, further boosting oxygen content. Moreover, the inner upconversion nanostructures as the near infrared (NIR) light-transducers enable to activate photosensitizers for deep-tissue PDT. Systematic experiments demonstrate that this suppressing O₂-consumption and O₂-generation strategy improved oxygen supply to boost the singlet oxygen generation to eradicate cancer cells under NIR light excitation. Better still, superior trimodality imaging capabilities (computed tomography (CT), NIR-II window fluorescence, and tumor microenvironment-responsive T1-weighted magnetic resonance (MR) imaging) of the nanoplatform were evaluated. Our findings offer a promising aproach to conquer the serious hypoxia problem in cancer therapy by turning down the O₂ metabolism aveneue and simultaneously generating O₂.

Keywords: Hypoxia; Photodynamic therapy; Respiration inhibition; Tumor; Upconversion.