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Hybrid Nanomedicine Fabricated from Photosensitizer‐Terminated Metal–Organic Framework Nanoparticles for Photodynamic Therapy and Hypoxia‐Activated Cascade Chemotherapy
Zhimei He1; Yunlu Dai2; Xiangli Li1; Dan Guo1; Yijing Liu3; Xiaolin Huang3; Jingjing Jiang4; Sheng Wang3; Guizhi Zhu3; Fuwu Zhang3; Lisen Lin3; Jun‐Jie Zhu1; Guocan Yu3; Xiaoyuan Chen3
2018
Source Publicationsmall
ISSN1613-6810
Volume15Issue:4
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.

KeywordBanoxantrone Cascade Therapy Hypoxia‐activated Prodrugs Nanoscale Metal–organic Frameworks Photodynamic Therapy
DOIhttps://doi.org/10.1002/smll.201804131
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Language英语
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Document TypeJournal article
CollectionFaculty of Health Sciences
Affiliation1.State Key Laboratory of Analytical Chemistry for Life ScienceSchool of Chemistry and Chemical EngineeringNanjing UniversityNanjing 210023, P. R. China
2.Faculty of Health SciencesUniversity of MacauMacau SAR 999078, P. R. China
3.Laboratory of Molecular Imaging and Nanomedicine (LOMIN)National Institute of Biomedical Imaging and Bioengineering (NIBIB)National Institutes of Health (NIH)Bethesda, MD 20892, USA
4.State Key Laboratory of Coordination ChemistrySchool of Chemistry and Chemical EngineeringNanjing UniversityNanjing 210023, P. R. China
Recommended Citation
GB/T 7714
Zhimei He,Yunlu Dai,Xiangli Li,et al. Hybrid Nanomedicine Fabricated from Photosensitizer‐Terminated Metal–Organic Framework Nanoparticles for Photodynamic Therapy and Hypoxia‐Activated Cascade Chemotherapy[J]. small,2018,15(4).
APA Zhimei He.,Yunlu Dai.,Xiangli Li.,Dan Guo.,Yijing Liu.,...&Xiaoyuan Chen.(2018).Hybrid Nanomedicine Fabricated from Photosensitizer‐Terminated Metal–Organic Framework Nanoparticles for Photodynamic Therapy and Hypoxia‐Activated Cascade Chemotherapy.small,15(4).
MLA Zhimei He,et al."Hybrid Nanomedicine Fabricated from Photosensitizer‐Terminated Metal–Organic Framework Nanoparticles for Photodynamic Therapy and Hypoxia‐Activated Cascade Chemotherapy".small 15.4(2018).
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