Academia Journal
Journal of Controlled Release
Volume 326, 10 October 2020, Pages 442-454
Impact Factor: 7.633
Author
Abhishek Sahua, Kiyoon Mina, Investigation Jin Jeon, Investigation Hee Seok Yangb c, Investigation, Resources Giyoong Tae a'*
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 Pluroniccoated nanographene oxide through simple hydrophobic interaction and JT—JT stacking. The nanosystem showed high cellular uptake in the breast cancer cells but did not show any cytotoxicity in the dark condition. nGOhemin-Ce6 showed efficient 02 generation capacity in the presence of H202, 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 02 generation capability. Upon intravenous administration, nGOhemin-Ce6 nanosystem showed high tumor accumulation through passive targeting owing to their small size 50 nm). Within the tumor, hemin generated 02 from the endogenous H202 and attenuated hypoxia as evidenced by the reduced expression of HIF-1a, a prominent hypoxia marker. Meanwhile, catalytically generated 02 markedly improved the therapeutic efficiency of PDT in a mouse tumor xenograft model by aiding the lightinduced ROS production by Ce6. Compared to a control nanosystem without hemin (nGO—Ce6), the catalytic nanosystem of nGO-hemin-Ce6 exhibited significantly higher tumor suppression ability.
Keywords
Graphene oxide, Hypoxia, Hemin, Catalase mimetic, Photodynamic therapy