# A TEMPO-loaded DNA hydrogel enabling integrated early diagnosis and treatment of osteoarthritis

**Authors:** Hong Huang, Mingze Tang, Pengcheng Hu, Yingshi Zhan, Wei Sun, Weipeng Zheng, Jianwei Zhu, Jianmao Chen, Song Xue, Shiqian Huang, Weiyu Han, Chao Zhang, Changhai Ding, Yan Zhang, Shushu Li, Guangfeng Ruan

PMC · DOI: 10.1186/s12951-025-03794-0 · Journal of Nanobiotechnology · 2025-10-31

## TL;DR

A new DNA hydrogel loaded with an antioxidant can both detect and treat osteoarthritis at an early stage.

## Contribution

A multifunctional hydrogel is developed for integrated early diagnosis and treatment of osteoarthritis.

## Key findings

- TEMPO@DSH reduces chondrocyte senescence by inhibiting NF-κB and mTOR pathways.
- The hydrogel enables MRI-based detection of ROS levels for early osteoarthritis diagnosis.
- The material offers a dual therapeutic and diagnostic platform for osteoarthritis management.

## Abstract

Osteoarthritis (OA) is a chronic inflammatory disease characterized primarily by cartilage degradation. Current imaging techniques often detect OA only after irreversible cartilage damage has occurred, and no drugs are available to halt disease progression. Early diagnosis and intervention may serve as an effective strategy to delay OA advancement. In this study, we developed a multifunctional material TEMPO@DSH by encapsulating 2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO), a reactive oxygen species (ROS)-responsive antioxidant, within anti-inflammatory DNA supramolecular hydrogel (DSH). TEMPO@DSH mitigates oxidative stress-induced mitochondrial damage in chondrocytes and inhibits the NF-κB and mTOR pathways, thereby reducing chondrocyte senescence and exerting therapeutic effects against OA. Additionally, by taking advantage of the loss of paramagnetism of TEMPO after reacting with ROS, magnetic resonance imaging following intra-articular injection of TEMPO@DSH can reflect the local levels of ROS in the joint. Given that elevated ROS levels precede observable imaging changes in early-stage OA, this approach enables early diagnosis. Overall, TEMPO@DSH serves as an integrated platform for the early diagnosis and treatment of OA, potentially offering a novel strategy for effective disease management.

The online version contains supplementary material available at 10.1186/s12951-025-03794-0.

## Linked entities

- **Chemicals:** 2,2,6,6-tetramethylpiperidine 1-oxyl (PubChem CID 549976)
- **Diseases:** osteoarthritis (MONDO:0005178)

## Full-text entities

- **Genes:** MTOR (mechanistic target of rapamycin kinase) [NCBI Gene 2475] {aka FRAP, FRAP1, FRAP2, RAFT1, RAPT1, SKS}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}
- **Diseases:** cartilage damage (MESH:D002357), OA (MESH:D010003), inflammatory (MESH:D007249), mitochondrial damage (MESH:D028361)
- **Chemicals:** ROS (MESH:D017382), 2,2,6,6-tetramethylpiperidine 1-oxyl (MESH:C003959), TEMPO@DSH (-)

## Full text

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## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12577105/full.md

## References

8 references — full list in the complete paper: https://tomesphere.com/paper/PMC12577105/full.md

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Source: https://tomesphere.com/paper/PMC12577105