Catalytic nanographene oxide with hemin for enhanced photodynamic therapy.

Abstract

Hypoxia is a hallmark of many malignant solid tumors. The inadequate oxygen concentration in the hypoxic regions of a solid tumor impedes the efficiency of photodynamic therapy (PDT) because the generation of reactive oxygen species during the PDT process is directly dependent on the available oxygen. To enhance the therapeutic efficacy of PDT, we have developed a novel catalytic nanoplatform (nGO-hemin-Ce6) by co-encapsulating hemin as a catalase-mimetic nanozyme and chlorin e6 (Ce6) as a photosensitizer into Pluronic-coated nanographene oxide through simple hydrophobic interaction and π-π stacking. The nanosystem showed high cellular uptake in the breast cancer cells but did not show any cytotoxicity in the dark condition. nGO-hemin-Ce6 showed efficient O2 generation capacity in the presence of H2O2, through the catalase-mimetic activity of hemin. In the in vitro cell experiments, only nGO-hemin-Ce6 could show comparable PDT effect in normoxia as well as hypoxia due to the in situ O2 generation capability. Upon intravenous administration, nGO-hemin-Ce6 nanosystem showed high tumor accumulation through passive targeting owing to their small size (~ 50 nm). Within the tumor, hemin generated O2 from the endogenous H2O2 and attenuated hypoxia as evidenced by the reduced expression of HIF-1α, a prominent hypoxia marker. Meanwhile, catalytically generated O2 markedly improved the therapeutic efficiency of PDT in a mouse tumor xenograft model by aiding the light-induced ROS production by Ce6. Compared to a control nanosystem without hemin (nGOCe6), the catalytic nanosystem of nGO-hemin-Ce6 exhibited significantly higher tumor suppression ability.

• Authors: Abhishek Sahu, Kiyoon Min, Jin Jeon, Hee Seok Yang, Giyoong Tae
• Journal: Journal of controlled release : official journal of the Controlled Release Society (J Control Release) Vol. 326 Pg. 442-454 (10 10 2020) ISSN: 1873-4995 [Electronic] Netherlands
• PMID: 32726649 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020. Published by Elsevier B.V.

Chemical References

• Oxides
• Photosensitizing Agents
• Porphyrins
• Hemin
• Hydrogen Peroxide

Topics

• Animals
• Cell Line, Tumor
• Hemin
• Hydrogen Peroxide
• Mice
• Oxides
• Photochemotherapy
• Photosensitizing Agents
• Porphyrins