Disruption of Iron Homeostasis to Induce Ferroptosis with Albumin‐Encapsulated Pt(IV) Nanodrug for the Treatment of Non‐Small Cell Lung Cancer

Author:

Tian Hui‐Xiang123ORCID,Mei Jie34567ORCID,Cao Lei13,Song Jianan7,Rong Dingchao8,Fang Man1,Xu Zhe1,Chen Juan1,Tang Jie3456,Xiao Haihua9,Liu Zhaoqian3456,Wang Peng‐Yuan7ORCID,Yin Ji‐Ye3456,Li Xiang‐Ping13ORCID

Affiliation:

1. Department of Pharmacy Xiangya Hospital Central South University Changsha 410008 China

2. School of Bioscience and Bioengineering South China University of Technology Guangzhou 510006 China

3. National Clinical Research Center for Geriatric Disorders Xiangya Hospital Central South University Changsha 410008 China

4. Department of Clinical Pharmacology Xiangya Hospital Central South University Changsha 410008 China

5. Institute of Clinical Pharmacology Hunan Key Laboratory of Pharmacogenetics Central South University Changsha 410008 China

6. Engineering Research Center of Applied Technology of Pharmacogenomics Ministry of Education 110 Xiangya Road Changsha 410008 China

7. Oujiang Laboratory Key Laboratory of Alzheimer's Disease of Zhejiang Province Institute of Aging Wenzhou Medical University Wenzhou 325000 China

8. Department of Orthopaedic Surgery The Third Affiliated Hospital Guangzhou Medical University Guangzhou 510150 China

9. Beijing National Laboratory for Molecular Sciences State Key Laboratory of Polymer Physics and Polymer Chemistry Institute of Chemistry Chinese Academy of Sciences Beijing 100190 China

Abstract

AbstractNon‐small cell lung cancer (NSCLC) is the most common pathological type of lung cancer , accounting for approximately 85% of lung cancers. For more than 40 years, platinum (Pt)‐based drugs are still one of the most widely used anticancer drugs even in the era of precision medicine and immunotherapy. However, the clinical limitations of Pt‐based drugs, such as serious side effects and drug resistance, have not been well solved. This study constructs a new albumin‐encapsulated Pt(IV) nanodrug (HSA@Pt(IV)) based on the Pt(IV) drug and nanodelivery system. The characterization of nanodrug and biological experiments demonstrate its excellent drug delivery and antitumor effects. The multi‐omics analysis of the transcriptome and the ionome reveals that nanodrug can activate ferroptosis by affecting intracellular iron homeostasis in NSCLC. This study provides experimental evidence to suggest the potential of HSA@Pt(IV) as a nanodrug with clinical application.

Funder

Health Commission of Hunan Province

National Natural Science Foundation of China

Publisher

Wiley

Subject

Biomaterials,Biotechnology,General Materials Science,General Chemistry

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