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iRGD 与索拉非尼负载铁基金属有机骨架联合应用作为肝癌治疗的靶向铁死亡剂。

Co-Administration of iRGD with Sorafenib-Loaded Iron-Based Metal-Organic Framework as a Targeted Ferroptosis Agent for Liver Cancer Therapy.

机构信息

Department of Radiology and Key Laboratory of Diagnostic Imaging and Interventional Radiology of Liaoning Province, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, People's Republic of China.

Laboratory of Controllable Preparation and Application of Nanomaterials, Laboratory of Cryogenics, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing, People's Republic of China.

出版信息

Int J Nanomedicine. 2021 Feb 11;16:1037-1050. doi: 10.2147/IJN.S292528. eCollection 2021.

DOI:10.2147/IJN.S292528
PMID:33603367
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7884959/
Abstract

PURPOSE

Hepatocellular carcinoma (HCC) is one of the most common fatal cancers, with no curative therapy available. The concept of ferroptosis is attracting increasing attention in cancer research. Herein, we describe the use of a nanodevice as an effective strategy for inducing ferroptosis to manage HCC.

METHODS

To improve ferroptosis-induced treatment of HCC, we constructed sorafenib (sor)-loaded MIL-101(Fe) nanoparticles (NPs) [MIL-101(Fe)@sor] and evaluated the efficacy of ferroptosis-based HCC therapy after co-administration with the iRGD peptide both in vitro and in vivo.

RESULTS

The prepared MIL-101(Fe) NPs have several promising characteristics including drug-loading, controllable release, peroxidase activity, biocompatibility, and T2 magnetic resonance imaging ability. MIL-101(Fe)@sor NPs significantly induced ferroptosis in HepG2 cells, increased the levels of lipid peroxidation and malondialdehyde, and reduced those of glutathione and glutathione peroxidase 4 (GPX-4). The in vivo results showed that the MIL-101(Fe)@sor NPs significantly inhibited tumor progression and decreased GPX-4 expression levels, with negligible long-term toxicity. Meanwhile, co-administration of MIL-101(Fe)@sor NPs with iRGD significantly accelerated ferroptosis.

CONCLUSION

Our findings suggest that MIL-101(Fe)@sor NPs co-administered with iRGD are a promising strategy for inducing HCC ferroptosis.

摘要

目的

肝细胞癌（HCC）是最常见的致命癌症之一，目前尚无有效的治疗方法。铁死亡的概念在癌症研究中越来越受到关注。本文描述了一种纳米器件作为一种有效的诱导铁死亡策略来治疗 HCC。

方法

为了提高铁死亡诱导治疗 HCC 的效果，我们构建了索拉非尼（sor）负载的 MIL-101(Fe) 纳米粒子（NPs）[MIL-101(Fe)@sor]，并评估了在与 iRGD 肽共同给药后，基于铁死亡的 HCC 治疗的效果，无论是在体外还是体内。

结果

所制备的 MIL-101(Fe) NPs 具有几种有前途的特性，包括载药、可控释放、过氧化物酶活性、生物相容性和 T2 磁共振成像能力。MIL-101(Fe)@sor NPs 可显著诱导 HepG2 细胞发生铁死亡，增加脂质过氧化和丙二醛水平，降低谷胱甘肽和谷胱甘肽过氧化物酶 4（GPX-4）水平。体内结果表明，MIL-101(Fe)@sor NPs 可显著抑制肿瘤进展并降低 GPX-4 表达水平，且长期毒性可忽略不计。同时，MIL-101(Fe)@sor NPs 与 iRGD 联合给药可显著加速铁死亡。

结论

我们的研究结果表明，MIL-101(Fe)@sor NPs 联合 iRGD 是一种很有前途的诱导 HCC 铁死亡的策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3031/7884959/02edc09d7c29/IJN-16-1037-g0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3031/7884959/d098c7eb0e34/IJN-16-1037-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3031/7884959/f8fad2eac4e6/IJN-16-1037-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3031/7884959/29c971e27ec8/IJN-16-1037-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3031/7884959/8e5d02ab72b8/IJN-16-1037-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3031/7884959/2143c9e556c8/IJN-16-1037-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3031/7884959/787b99cd620f/IJN-16-1037-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3031/7884959/0bb95e240b54/IJN-16-1037-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3031/7884959/02edc09d7c29/IJN-16-1037-g0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3031/7884959/d098c7eb0e34/IJN-16-1037-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3031/7884959/f8fad2eac4e6/IJN-16-1037-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3031/7884959/29c971e27ec8/IJN-16-1037-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3031/7884959/8e5d02ab72b8/IJN-16-1037-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3031/7884959/2143c9e556c8/IJN-16-1037-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3031/7884959/787b99cd620f/IJN-16-1037-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3031/7884959/0bb95e240b54/IJN-16-1037-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3031/7884959/02edc09d7c29/IJN-16-1037-g0008.jpg

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