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Research Article

Protein-based nanocarriers for efficient Etoposide delivery and cancer therapy

Bo Wang1,§Xiaoxiong Xu1,§Bo Li2Zheng Wei3,4Shuang Lu3Jingjing Li3Kai Liu2Hongjie Zhang2,3Fan Wang3( )Yang Yang1,5( )
Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai 200433, China
Engineering Research Center of Advanced Rare Earth Materials, (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084, China
State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China
University of Science and Technology of China, Hefei 230026, China
School of Materials Science and Engineering, Tongji University, Shanghai 201804, China

§ Bo Wang and Xiaoxiong Xu contributed equally to this work.

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Graphical Abstract

A new type of biosynthetic and unfolded protein nanocarrier was designed and fabricated to load and deliver etoposide. The protein-based nanodrug showed prolonged half-life, higher biocompatibility, superior anti-tumor effect, and low immunogenicity when compared with the pristine drug.


Etoposide, a DNA damage-inducing agent, is widely used for malignant tumors. However, insufficient solubility, poor bioavailability and adverse events limited the treatment outcomes and prognosis. To address this, we here developed a novel biosynthetic and unfolded protein nanocarrier to load and deliver Etoposide. Compared with the pristine agent, the loading efficiency of the nanoformulated drug increased four times and the half-life time increased to 17.6 h with controlled release of the Etoposide for 6 days. The half-maximal inhibitory concentration at 48 h was lower than that at 24 h, suggesting a long-acting anti-tumor property. Moreover, the anti-tumor performance in rat models was significantly enhanced by improving solubility and cellular internalization. Additionally, immunogenicity and adverse toxicologic effects such as kidney and liver toxicity were significantly weakened. Therefore, the assembly strategy enables etoposide with higher efficacy, bioavailability, and safety, and has great potential in the comprehensive treatment of malignant tumors.

Electronic Supplementary Material (ESM)

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12274_2023_5841_MOESM1_ESM.pdf (584.9 KB)
Nano Research
Pages 11216-11220
Cite this article:
Wang B, Xu X, Li B, et al. Protein-based nanocarriers for efficient Etoposide delivery and cancer therapy. Nano Research, 2023, 16(8): 11216-11220.






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Received: 03 April 2023
Revised: 11 May 2023
Accepted: 12 May 2023
Published: 09 June 2023
© Tsinghua University Press 2023