COX-2 Inhibition mediated anti-angiogenic activatable prodrug potentiates cancer therapy in preclinical models

Biomaterials
Hyeong Seok KimJong Seung Kim

Abstract

Anti-angiogenesis, i.e., blocking the angiogenic pathway, has been considered as an important component in current cancer therapeutic modalities. However, the associated benefits have proven to be modest as tumor angiogenesis and regrowth persist, probably due to other ill-defined complex angiogenic mechanisms. Herein, we developed an indomethacin (IMC) incorporating system to mediate hypoxia responsive prodrug (TA) and diagnostic agent (DA) in cancer theranostic applications. Cyclooxygenase 2 (COX-2) elevated expression in several cancer types is closely associated with severe tumor supporting vascularization factors. Our strategy utilizing COX-2 inhibition augmented the anti-angiogenetic induced hypoxia responsive prodrug activation well. Both in vitro and in vivo results proved that DA and TA exhibited specificity towards COX-2 positive (+ve) HeLa and A549 cancer cell lines and activation under hypoxic conditions. Compared with controls (R1, and anticancer drug SN-38), TA displayed prolonged tumor retention and enhanced therapeutic efficacy in xenograft mouse models at a reduced dosage. Our results significantly highlighted the importance of COX-2 blockade mediated anti-angiogenesis in complementing the hypoxia-responsive dr...Continue Reading

Citations

Nov 30, 2018·Chembiochem : a European Journal of Chemical Biology·Hardev SinghJong Seung Kim
Jan 11, 2019·Angewandte Chemie·Wen-Chao GengDong-Sheng Guo
Oct 4, 2019·Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology·Xu Zhen, Xiqun Jiang
Dec 24, 2018·Chemical Society Reviews·Amit SharmaJong Seung Kim
Apr 11, 2020·Oxidative Medicine and Cellular Longevity·Yinghong ZhouJingtao Zhong
Sep 12, 2019·Journal of the American Chemical Society·Amit SharmaJong Seung Kim

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