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Research Article

Co-delivery of luteolin and TGF-β1 plasmids with ROS-responsive virus-inspired nanoparticles for microenvironment regulation and chemo-gene therapy of intervertebral disc degeneration

Yifan Ding1,§, Huan Wang1,§, Yunyun Wang3, Long Li1, Jiahui Ding2, Caiyan Yuan2, Tao Xu1, Haoran Xu1, Hui Xie4, Ning Zhu5,6, Xin Hu6,7, Huang Fang1( ), Songwei Tan2( )
Department of Orthopedic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
Department of Cardiology, the Fifth Hospital in Wuhan, Wuhan 430030, China
Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing 211800, China
State Key Laboratory of Materials-Oriented Chemical Engineering, Nanjing Tech University, Nanjing 211800, China
College of Materials Science and Engineering, Nanjing Tech University, Nanjing 211800, China

§ Yifan Ding and Huan Wang contributed equally to this work.

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Graphical Abstract

A reactive oxygen species (ROS)-responsive nanoplatform (LUT-pTGF-β1@PBC) was constructed for LUT-TGF-β1 plasmid combinatorial therapy of intervertebral disc degeneration (IDD).

Abstract

Intervertebral disc degeneration (IDD) is closely related to inflammation and imbalance of synthesis/catabolism of extracellular matrix (ECM) in intervertebral disc (IVD). Considering this, luteolin (LUT), a kind of natural flavonoid with good anti-inflammatory effect and TGF-β1 (a gene that promotes the regeneration of ECM) plasmid was co-loaded and co-delivered to nucleus pulposus cells (NPCs). Reactive oxygen species (ROS) responsive cationic copolymer, poly(β-amino ester)-poly(ε-caprolactone) (PBC), with high plasmid DNA (pDNA) compression affinity was synthesized. It can self-assemble into nano-sized polyplexes (pDNA@PBC) with virus-inspired structure and function through which it can transfect pDNA into NPCs with very high efficiency and negligible cytotoxicity. LUT was encapsulated in the hydrophobic core of pDNA@PBC. The co-delivery system, LUT-pTGF-β1@PBC, could enhance the cellular uptake of NPCs and manifest excellent sustained drug release in IVD. Real time quantitative polymerase chain reaction (RT-qPCR) and Western blot experiments reveal that the co-delivery system could inhibit inflammation in NPCs and restore the balance of anabolism and catabolism in vitro by activating TGF/SMAD3 and inhibiting NF-kB/p65. Moreover, LUT-pTGF-β1@PBC retards IDD in vivo as detected by radiological and histological methods with good biosafety in rats. LUT-pTGF-β1@PBC may be a promising option for the treatment of IDD.

Keywords

intervertebral disc degenerationpoly(β-amino ester)luteolinTGF-β1co-delivery

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Nano Research
Volume 15 Issue 9,
September 2022
Pages 8214-8227
DOI: 10.1007/s12274-022-4285-7
Cite this article:
Ding Y, Wang H, Wang Y, et al. Co-delivery of luteolin and TGF-β1 plasmids with ROS-responsive virus-inspired nanoparticles for microenvironment regulation and chemo-gene therapy of intervertebral disc degeneration. Nano Research, 2022, 15(9): 8214-8227. https://doi.org/10.1007/s12274-022-4285-7
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Received: 17 January 2022
Revised: 01 March 2022
Accepted: 01 March 2022
Published: 11 May 2022
© Tsinghua University Press 2022
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