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

Suo，Meng1; Liu，Zeming2; Tang，Wenxue3; Guo，Jiancheng3; Jiang，Wei4; Liu，Ying3; Duo，Yanhong5

2020-11-26

10.1039/d0nr06594c

Nanoscale   影响因子和分区

2040-3364

2040-3372

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 hypoxia-related resistance to RT, thereby providing a framework for the design of potent radiosensitizing therapeutic approaches.

SCI ; EI

英语

其他

National Natural Science Foundation of China[81901882] ; China Postdoctoral Science Foundation[2019M663062] ; Education Department of Henan Province[20A430026]

Chemistry ; Science & Technology - Other Topics ; Materials Science ; Physics

Chemistry, Multidisciplinary ; Nanoscience & Nanotechnology ; Materials Science, Multidisciplinary ; Physics, Applied

WOS:000593021300040

ROYAL SOC CHEMISTRY

2-s2.0-85096886316

Scopus

1.Department of Molecular pathology,Application Center for Precision Medicine,Second Affiliated Hospital of Zhengzhou University,Zhengzhou,450052,China
2.Department of Plastic Surgery,Zhongnan Hospital of Wuhan University,Wuhan,430071,China
3.Department of Molecular pathology, Application Center for Precision Medicine, the Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China. weijiang@zzu.edu.cn lydyzjj@163.com and Center for Precision Medicine, Academy of Medical Sciences, Zhengzhou University, Zhengzhou 450001, China
4.Department of Molecular pathology, Application Center for Precision Medicine, the Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China. lydyzjj@163.com and Center for Precision Medicine, Academy of Medical Sciences, Zhengzhou University, Zhengzhou 450001, China
5.Department of Radiation Oncology,Second Clinical Medical College of Jinan University,1st Affiliated Hospital of Southern University of Science and Technology,Shenzhen People's Hospital,Shenzhen,518020,China

Suo，Meng,Liu，Zeming,Tang，Wenxue,et al. 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[J]. Nanoscale,2020,12(45):23259-23265.

Suo，Meng.,Liu，Zeming.,Tang，Wenxue.,Guo，Jiancheng.,Jiang，Wei.,...&Duo，Yanhong.(2020).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,12(45),23259-23265.

Suo，Meng,et al."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 12.45(2020):23259-23265.