Hybrid Nanomedicine Fabricated from Photosensitizer-Terminated Metal-Organic Framework Nanoparticles for Photodynamic Therapy and Hypoxia-Activated Cascade Chemotherapy.

Abstract

During photodynamic therapy (PDT), severe hypoxia often occurs as an undesirable limitation of PDT owing to the O2 -consuming photodynamic process, compromising the effectiveness of PDT. To overcome this problem, several strategies aiming to improve tumor oxygenation are developed. Unlike these traditional approaches, an opposite method combining hypoxia-activated prodrug and PDT may provide a promising strategy for cancer synergistic therapy. In light of this, azido-/photosensitizer-terminated UiO-66 nanoscale metal-organic frameworks (UiO-66-H/N3 NMOFs) which serve as nanocarriers for the bioreductive prodrug banoxantrone (AQ4N) are engineered. Owing to the effective shielding of the nanoparticles, the stability of AQ4N is well preserved, highlighting the vital function of the nanocarriers. By virtue of strain-promoted azide-alkyne cycloaddition, the nanocarriers are further decorated with a dense PEG layer to enhance their dispersion in the physiological environment and improve their therapeutic performance. Both in vitro and in vivo studies reveal that the O2 -depleting PDT process indeed aggravates intracellular/tumor hypoxia that activates the cytotoxicity of AQ4N through a cascade process, consequently achieving PDT-induced and hypoxia-activated synergistic therapy. Benefiting from the localized therapeutic effect of PDT and hypoxia-activated cytotoxicity of AQ4N, this hybrid nanomedicine exhibits enhanced therapeutic efficacy with negligible systemic toxicity, making it a promising candidate for cancer therapy.

• Authors: Zhimei He, Yunlu Dai, Xiangli Li, Dan Guo, Yijing Liu, Xiaolin Huang, Jingjing Jiang, Sheng Wang, Guizhi Zhu, Fuwu Zhang, Lisen Lin, Jun-Jie Zhu, Guocan Yu, Xiaoyuan Chen
• Journal: Small (Weinheim an der Bergstrasse, Germany) (Small) Vol. 15 Issue 4 Pg. e1804131 (01 2019) ISSN: 1613-6829 [Electronic] Germany
• PMID: 30565431 (Publication Type: Journal Article, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical References

• HIF1A protein, human
• Hypoxia-Inducible Factor 1, alpha Subunit
• Photosensitizing Agents

Topics

• Cell Line, Tumor
• Cell Survival (drug effects)
• Flow Cytometry
• Humans
• Hypoxia-Inducible Factor 1, alpha Subunit (metabolism)
• Microscopy, Confocal
• Microscopy, Electron, Scanning
• Microscopy, Electron, Transmission
• Microscopy, Fluorescence
• Nanomedicine (methods)
• Nanoparticles (chemistry, ultrastructure)
• Neoplasms (metabolism)
• Photochemotherapy (methods)
• Photosensitizing Agents (chemistry)