Pathological microenvironment-responsive nano-glycospheres restore disc homeostasis by combinatorial metabolic and genetic regulation.
8 affiliations
- 1Guangdong Provincial Key Laboratory of Advanced Biomaterials, Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, 518055, People's Republic of China.
- 2Department of Orthopaedics, Qilu Hospital of Shandong University, Jinan, 250012, People's Republic of China.
- 3Department of Spine Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, People's Republic of China.
- 4Pain Research Center, Sun Yat-sen University, Guangzhou, 510080, People's Republic of China.
- 5Department of Spine Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, People's Republic of China. [email protected].
- 6Pain Research Center, Sun Yat-sen University, Guangzhou, 510080, People's Republic of China. [email protected].
- 7Guangdong Provincial Key Laboratory of Advanced Biomaterials, Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, 518055, People's Republic of China. [email protected].
- 8Guangdong Provincial Key Laboratory of Advanced Biomaterials, Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, 518055, People's Republic of China. [email protected].
Abstract
Intervertebral disc degeneration (IVDD) is fundamentally driven by a self-perpetuating pathological loop involving metabolic derangement, oxidative stress, and enzymatic hyper-activity. Conventional mono-therapies often fall short of reversing this complex microenvironmental collapse. Here, we developed a smart nano-glycosphere (siMMP13/2-DG NPs) designed for dual-track intervention to restore disc homeostasis. This responsive platform utilized a 2-deoxy-D-glucose (2-DG) shell crosslinked via reactive oxygen-sensitive phenylboronic acid moieties, enabling the simultaneous suppression of pathological glycolysis and the neutralization of oxidative stress. Concomitantly, the precise delivery of siMMP13 effectively silenced major catabolic enzymes, thereby arresting extracellular matrix degradation. Our findings demonstrated that this combinatorial approach effectively interrupted the lactate-driven inflammatory cascade, shifting the microenvironment from a hostile catabolic state toward a pro-regenerative metabolic balance. In the lumbar disc degeneration model, the siMMP13/2-DG NPs significantly preserved structural integrity and alleviated discogenic pain by dampening neuro-inflammatory signaling. By integrating metabolic reprogramming with targeted gene silencing, this study establishes a versatile therapeutic paradigm for the precision management of IVDD and offers broader insights into the treatment of other microenvironment-mediated musculoskeletal disorders.
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BibTeX
@article{zhao2026pathological,
title = {{Pathological microenvironment-responsive nano-glycospheres restore disc homeostasis by combinatorial metabolic and genetic regulation.}},
author = {Lei Zhao and Wenzheng Ma and Wantao Wang and Dan Zhou and Jinghao Fan and Mingkang Liu and Lei Liu and Lin Huang and Xue Wei and Zhaomin Zheng and Hongmei Liu and Decheng Wu},
journal = {Journal of nanobiotechnology},
year = {2026},
month = jul,
doi = {10.1186/s12951-026-04830-3},
url = {https://europepmc.org/article/MED/42894235},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Pathological microenvironment-responsive nano-glycospheres restore disc homeostasis by combinatorial metabolic and genetic regulation.
AU - Lei Zhao
AU - Wenzheng Ma
AU - Wantao Wang
AU - Dan Zhou
AU - Jinghao Fan
AU - Mingkang Liu
AU - Lei Liu
AU - Lin Huang
AU - Xue Wei
AU - Zhaomin Zheng
AU - Hongmei Liu
AU - Decheng Wu
PY - 2026
DA - 2026/07/01
JO - Journal of nanobiotechnology
DO - 10.1186/s12951-026-04830-3
UR - https://europepmc.org/article/MED/42894235
AB - Intervertebral disc degeneration (IVDD) is fundamentally driven by a self-perpetuating pathological loop involving metabolic derangement, oxidative stress, and enzymatic hyper-activity. Conventional mono-therapies often fall short of reversing this complex microenvironmental collapse. Here, we developed a smart nano-glycosphere (siMMP13/2-DG NPs) designed for dual-track intervention to restore disc homeostasis. This responsive platform utilized a 2-deoxy-D-glucose (2-DG) shell crosslinked via reactive oxygen-sensitive phenylboronic acid moieties, enabling the simultaneous suppression of pathological glycolysis and the neutralization of oxidative stress. Concomitantly, the precise delivery of siMMP13 effectively silenced major catabolic enzymes, thereby arresting extracellular matrix degradation. Our findings demonstrated that this combinatorial approach effectively interrupted the lactate-driven inflammatory cascade, shifting the microenvironment from a hostile catabolic state toward a pro-regenerative metabolic balance. In the lumbar disc degeneration model, the siMMP13/2-DG NPs significantly preserved structural integrity and alleviated discogenic pain by dampening neuro-inflammatory signaling. By integrating metabolic reprogramming with targeted gene silencing, this study establishes a versatile therapeutic paradigm for the precision management of IVDD and offers broader insights into the treatment of other microenvironment-mediated musculoskeletal disorders.
SN - 1477-3155
ER -