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

Autor: Yan L; The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan 523808, China., Chen Y; 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., Zhang S; 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., Zhu C; School of Basic Medicine Guangdong Medical University, Dongguan 523808, China., Xiao S; 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., Xia H; School of Basic Medicine Guangdong Medical University, Dongguan 523808, China., Chen X; Guangdong Provincial key Laboratory of Utilization and Conservation of Food and Medicinal Resources in Northern Region, Medical college, Shaoguan University, Shaoguan 512005, China., Guo D; Guangdong Provincial key Laboratory of Utilization and Conservation of Food and Medicinal Resources in Northern Region, Medical college, Shaoguan University, Shaoguan 512005, China., Lv X; 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., Rao L; 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., Zhuang M; 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.
Jazyk: angličtina
Zdroj: Nanomedicine : nanotechnology, biology, and medicine [Nanomedicine] 2024 Aug; Vol. 60, pp. 102758. Date of Electronic Publication: 2024 Jun 07.
DOI: 10.1016/j.nano.2024.102758
Abstrakt: 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.
Competing Interests: Declaration of competing interest The authors declare no potential conflict of interest.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: