Development of a novel oxidative stress-amplifying nanocomposite capable of supplying intratumoral H2O2 and O2 for enhanced chemodynamic therapy and radiotherapy in patient-derived xenograft (PDX) models.

Nanoscale
Meng SuoYanhong Duo

Abstract

Radiotherapy (RT) is a potent approach to cancer treatment, but the tumor microenvironment (TME) in solid tumors is often highly hypoxic and contains high levels of antioxidant enzymes, thereby reducing the RT efficacy. In this study, we developed an oxidative stress amplifier (termed CFM) capable of self-sufficient H2O2 and O2 delivery that can be used in concert with RT and chemodynamic therapy (CDT) to treat tumors in patient-derived xenograft (PDX) model systems. Upon exposure to the hypoxic and acidic TME, CFM undergoes rapid degradation that results in the release of Fe3+, Ca2+, O2, and H2O2. Glutathione can subsequently reduce Fe3+ to Fe2+, which is then able to react with H2O2via the Fenton reaction to yield high levels of hydroxyl radicals which subsequently damage mitochondria. CaO2-derived O2 also modulates intratumoral hypoxia, while excessive Ca2+ levels within mitochondria result in apoptotic cell death. Altogether, these properties sensitize PDX tumors to RT. Importantly, the Fe, Zn, and Ca generated by CFM degradation are essential elements in humans. Altogether, these properties make this approach to oxidative stress amplification a promising means of amplifying oxidative stress within tumors while overcoming h...Continue Reading

References

Nov 18, 2005·Toxicology Letters·Zhen ChenLijun Wan
May 27, 2008·Nature Reviews. Cancer·Mark W DewhirstBenjamin Moeller
Nov 21, 2008·Biomaterials·Se Heang OhBenjamin S Harrison
May 30, 2009·Nature Reviews. Drug Discovery·Dunyaporn TrachoothamPeng Huang
Jul 8, 2009·Arhiv za higijenu rada i toksikologiju·Vesna BenkovićNevenka Kopjar
Oct 3, 2009·Journal of the American Chemical Society·Chenjie XuShouheng Sun
Mar 25, 2011·Nature Reviews. Cancer·Adrian C BeggConchita Vens
Jan 31, 2012·Cellular Signalling·Paul D RayYoshiaki Tsuji
Oct 15, 2013·Journal of Cellular Biochemistry·Albert van der Vliet, Yvonne M W Janssen-Heininger
Jan 8, 2014·Nature Reviews. Endocrinology·Ida Pernicova, Márta Korbonits
Feb 25, 2014·Nature Reviews. Cancer·Katrina F Chu, Damian E Dupuy
Apr 18, 2019·Angewandte Chemie·Yuyan JiangKanyi Pu
May 22, 2019·Nature Biomedical Engineering·Qingle LiangXiangliang Yang
Oct 14, 2013·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Di ZhangHao Wang
May 27, 2020·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Daoming ZhuKaiyang Li

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Citations

Aug 17, 2021·Frontiers in Bioengineering and Biotechnology·Yiling YangJie Zhao

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Methods Mentioned

BETA
xenograft
dynamic light scattering
X-ray

Software Mentioned

Nano Measurer

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