DataVXACS NanoPaper
journal article·2018-11-27

Fenton-Reaction-Acceleratable Magnetic Nanoparticles for Ferroptosis Therapy of Orthotopic Brain Tumors

Zheyu Shen, Ting Liu, Yan Li, Joseph Lau, Zhen Yang, Wenpei Fan, Zijian Zhou, Changrong Shi, Chaomin Ke, Vladimir I. Bregadze, Swadhin K. Mandal, Yijing Liu, Zihou Li, Ting Xue, Guizhi Zhu, Jeeva Munasinghe, Gang Niu, Aiguo Wu, Xiaoyuan Chen

ACS Nano· Volume 12· Issue 11
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Source abstract

Abstract

Cancer is one of the leading causes of morbidity and mortality in the world, but more cancer therapies are needed to complement existing regimens due to problems of existing cancer therapies. Herein, we term ferroptosis therapy (FT) as a form of cancer therapy and hypothesize that the FT efficacy can be significantly improved via accelerating the Fenton reaction by simultaneously increasing the local concentrations of all reactants (Fe2+, Fe3+, and H2O2) in cancer cells. Thus, Fenton-reaction-acceleratable magnetic nanoparticles, i.e., cisplatin (CDDP)-loaded Fe3O4/Gd2O3 hybrid nanoparticles with conjugation of lactoferrin (LF) and RGD dimer (RGD2) (FeGd-HN@Pt@LF/RGD2), were exploited in this study for FT of orthotopic brain tumors. FeGd-HN@Pt@LF/RGD2 nanoparticles were able to cross the blood–brain barrier because of its small size (6.6 nm) and LF-receptor-mediated transcytosis. FeGd-HN@Pt@LF/RGD2 can be internalized into cancer cells by integrin αvβ3-mediated endocytosis and then release Fe2+, Fe3+, and CDDP upon endosomal uptake and degradation. Fe2+ and Fe3+ can directly participate in the Fenton reaction, whereas the CDDP can indirectly produce H2O2 to further accelerate the Fenton reaction. The acceleration of Fenton reaction generates reactive oxygen species to induce cancer cell death. FeGd-HN@Pt@LF/RGD2 successfully delivered reactants involved in the Fenton reaction to the tumor site and led to significant inhibition of tumor growth. Finally, the intrinsic magnetic resonance imaging (MRI) capability of the nanoparticles was used to assess and monitor tumor response to FT (self-MRI monitoring).
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Research context

Nanomaterials

OpenAlex topics: Nanoparticle-Based Drug Delivery · Extracellular vesicles in disease · Nanoplatforms for cancer theranostics

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

CAS Key Laboratory of Magnetic Materials and Devices, & Key Laboratory of Additive Manufacturing Materials of Zhejiang Province, & Division of Functional Materials and Nanodevices, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, 1219 Zhong-guan West Road, Ningbo, Zhejiang 315201, China

Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, Maryland 20892, United States

State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen 361102, China

College of Food and Pharmaceutical Sciences, Ningbo University, Ningbo 315211, China

A.N. Nesmeyanov Institute of Organoelement Compounds of Russian Academy of Sciences, Vavilov Str. 28, Moscow 119991, Russia

Department of Chemical Sciences, Indian Institute of Science Education and Research-Kolkata, Mohanpur 741246, India

Department of Pharmaceutics, School of Pharmacy, Massey Cancer Center, Virginia Commonwealth University, Richmond, Virginia 23298-0533, United States

Mouse Imaging Facility, National Institute of Neurological Disorder and Stroke, National Institutes of Health, Bethesda, Maryland 20892, United States

Funding

Ministry of Science and Technology of the People's Republic of China · Youth Innovation Promotion Association of the Chinese Academy of Sciences · National Institute of Biomedical Imaging and Bioengineering · Russian Foundation for Basic Research · Department of Science and Technology, Ministry of Science and Technology · National Natural Science Foundation of China · Natural Science Foundation of Zhejiang Province · Chinese Academy of Sciences · Zhejiang Province

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