2. Academic Validation
  3. Reconstruction of TNF-α with specific isoelectric point released from SPIONs basing on variable charge to enhance pH-sensitive controlled-release

Reconstruction of TNF-α with specific isoelectric point released from SPIONs basing on variable charge to enhance pH-sensitive controlled-release

  • Nanomedicine. 2024 Jun 7:60:102758. doi: 10.1016/j.nano.2024.102758.
Lin Yan 1,  Yadi Chen 2,  Shihao Zhang 2,  Chunjie Zhu 3,  Shangying Xiao 2,  Haishan Xia 3,  Xiaohua Chen 4,  Dan Guo 4,  Xiaohua Lv 2,  Lei Rao 5,  Manjiao Zhuang 6
Affiliations

Affiliations

  • 1 The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan 523808, China.
  • 2 Guangdong Key Laboratory for Research and Development of Natural Drugs, Dongguan Key Laboratory of Traditional Chinese Medicine and New Pharmaceutical Development, School of pharmacy, Guangdong Medical University, 523808, China.
  • 3 School of Basic Medicine Guangdong Medical University, Dongguan 523808, China.
  • 4 Guangdong Provincial key Laboratory of Utilization and Conservation of Food and Medicinal Resources in Northern Region, Medical college, Shaoguan University, Shaoguan 512005, China.
  • 5 Guangdong Provincial key Laboratory of Utilization and Conservation of Food and Medicinal Resources in Northern Region, Medical college, Shaoguan University, Shaoguan 512005, China; Department of Biomedicine, Chengdu Medical College, Chengdu 610500, China. Electronic address: 591617735@qq.com.
  • 6 The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan 523808, China; Guangdong Key Laboratory for Research and Development of Natural Drugs, Dongguan Key Laboratory of Traditional Chinese Medicine and New Pharmaceutical Development, School of pharmacy, Guangdong Medical University, 523808, China. Electronic address: man.jiao@163.com.
PMID: 38852881 DOI: 10.1016/j.nano.2024.102758
Abstract

The clinical application of tumor necrosis factor-α (TNF-α) is limited by its short half-life, subeffective concentration in the targeted area and severe systemic toxicity. In this study, the recombinant polypeptide S4-TNF-α was constructed and coupled with chitosan-modified superparamagnetic iron oxide nanoparticles (S4-TNF-α-SPIONs) to achieve pH-sensitive controlled release and active tumor targeting activity. The isoelectric point (pI) of S4-TNF-α was reconstructed to approach the pH of the tumor microenvironment. The negative-charge S4-TNF-α was adsorbed to chitosan-modified superparamagnetic iron oxide nanoparticles (CS-SPIONs) with a positive charge through electrostatic adsorption at physiological pH. The acidic tumor microenvironment endowed S4-TNF-α with a zero charge, which accelerated S4-TNF-α release from CS-SPIONs. Our studies showed that S4-TNF-α-SPIONs displayed an ideal pH-sensitive controlled release capacity and improved antitumor effects. Our study presents a novel approach to enhance the pH-sensitive controlled-release of genetically engineered drugs by adjusting their pI to match the pH of the tumor microenvironment.

Keywords

Isoelectric point; SPION; TNF-α; Tumor microenvironment; pH-sensitive controlled release.

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