Journal
NANO LETTERS
Volume 21, Issue 7, Pages 3218-3224Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.nanolett.1c00488
Keywords
Covalent organic framework; Photodynamic therapy; Hypoxia response; Drug delivery; Antitumor agents
Categories
Funding
- National Key R&D Program of China [2017YFA0701301, 2017YFA0205400]
- National Natural Science Foundation of China [51690153, 21720102005]
- Excellent Research Program of Nanjing University [ZYJH004]
- Fundamental Research Funds for the Central Universities
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COFs have been synthesized with hypoxia-responsive azo bonds containing photosensitizers and hypoxia-activated drugs for drug delivery. Upon exposure to hypoxic conditions and NIR light, the COF structure is disrupted, leading to drug release and activation of the hypoxia-activated drug, resulting in effective cancer cell killing and tumor growth inhibition.
Covalent organic frameworks (COFs) have received much attention in the biomedical area. However, little has been reported about stimuli-responsive COF for drug delivery. Herein, we synthesized a hypoxia-responsive azo bond-containing COF with nanoscale size and immobilized both photosensitizers chlorin e6 (Ce6) and hypoxia-activated drug tirapazamine (TPZ) into the COFs. When such a COF entered the hypoxic environment and tumor, the COF structure was ruptured and loaded drugs were released from the COF. Together, upon near-infrared (NIR) light irradiation, Ce6 consumed oxygen to produce cytotoxic reactive oxygen species, leading to elevated hypoxia. Such two-step hypoxia stimuli successively induced the deintegration of COF, drug release and activation of TPZ. This promoted the TPZ to generate massive biotoxic oxyradical. In vitro and in vivo evaluation indicated that this two-step hypoxia-activated COF drug delivery system could kill cancer cells and inhibit the growth of tumors effectively.
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