Fenton反应促进磁性纳米粒子治疗原位脑肿瘤的肥大症治疗,ACS Nano

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Fenton反应促进磁性纳米粒子治疗原位脑肿瘤的肥大症治疗
ACS Nano ( IF 15.8 ) Pub Date : 2018-10-30 00:00:00 , DOI: 10.1021/acsnano.8b06201
Zheyu Shen _{1,

2} , Ting Liu ₃ , Yan Li ₄ , Joseph Lau ₂ , Zhen Yang ₂ , Wenpei Fan ₂ , Zijian Zhou ₂ , Changrong Shi ₃ , Chaomin Ke ₃ , Vladimir I. Bregadze ₅ , Swadhin K. Mandal ₆ , Yijing Liu ₂ , Zihou Li ₁ , Ting Xue ₁ , Guizhi Zhu _{2,

7} , Jeeva Munasinghe ₈ , Gang Niu ₂ , Aiguo Wu ₁ , Xiaoyuan Chen ₂

Affiliation

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

癌症是世界上发病率和死亡率的主要原因之一，但是由于现有的癌症治疗方法存在问题，因此需要更多的癌症治疗方法来补充现有的治疗方案。在此，我们术语ferroptosis疗法（FT）作为癌症治疗和或推测的一种形式，所述FT药效可显著改善经由通过同时增加所有反应物的局部浓度（铁加速芬顿反应²⁺，铁³⁺，和H ₂ O ₂）。因此，Fenton可促进反应的磁性纳米颗粒，即顺铂（CDDP）负载的Fe ₃ O ₄ / Gd ₂ O ₃在这项研究中，利用乳铁蛋白（LF）和RGD二聚体（RGD2）（[电子邮件保护] @ LF / RGD2）结合的杂化纳米颗粒用于原位脑肿瘤的FT。LF / RGD2纳米粒子由于尺寸小（6.6 nm）和LF受体介导的胞吞作用而能够穿过血脑屏障。[电子邮件保护] @ LF / RGD2可以通过整合素α内化进入癌细胞_v β ₃ -介导的内吞作用和然后释放的Fe ²⁺，铁³⁺在核内体摄取和降解，和CDDP。Fe ²⁺和Fe ³⁺可以直接参与Fenton反应，而CDDP可以间接产生H ₂ O ₂进一步加速芬顿反应。Fenton反应的加速产生活性氧，从而诱导癌细胞死亡。[电子邮件保护] @ LF / RGD2成功地将参与Fenton反应的反应物传递到肿瘤部位，并显着抑制了肿瘤的生长。最后，纳米粒子的固有磁共振成像（MRI）能力用于评估和监测肿瘤对FT的反应（自我MRI监测）。

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

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) ([email protected]@LF/RGD2), were exploited in this study for FT of orthotopic brain tumors. [email protected]@LF/RGD2 nanoparticles were able to cross the blood–brain barrier because of its small size (6.6 nm) and LF-receptor-mediated transcytosis. [email protected]@LF/RGD2 can be internalized into cancer cells by integrin α_vβ₃-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. [email protected]@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).

更新日期：2018-10-30

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