A nanoengineered MSC therapeutic for synergistic therapy of lupus nephritis via cfDNA clearance and targeted immunomodulation.
4 affiliations
- 1Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
- 2Department of Rheumatology and Immunology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
- 3Department of Rheumatology and Immunology, The Second Affiliated Hospital of Anhui Medical University, Hefei, China.
- 4Research Institute for Biomaterials, Tech Institute for Advanced Materials, College of Materials Science and Engineering, Suqian Advanced Materials Industry Technology Innovation Center, Nanjing Tech University, Nanjing 211816, China.
Abstract
Rationale
Lupus nephritis (LN) remains a clinical challenge due to the dose-limiting toxicity of conventional immunosuppressants and the poor engraftment/efficacy of mesenchymal stromal cell (MSC) therapies.Methods
We report a novel nanoengineered MSC therapeutic for LN by engineering MSCs with a cell-free DNA (cfDNA)-targeting dendritic nanogel. To obtain the hybrid MSC-G3K@T system, we coupled tacrolimus-loaded, disulfide-crosslinked polylysine dendrimer nanogels (G3K@T) onto the MSC membrane. Our system exploits two synergistic targeting strategies: the innate homing capacity of MSCs, plus the specific affinity of the cationic G3K dendrimer for anionic cfDNA, which enriches in inflamed kidneys.Results
Our system acts through two coordinated actions: the nanogel responds to the oxidative renal microenvironment and releases tacrolimus in a spatiotemporally controlled manner, thereby suppressing T-cell activation. At the same time, it scavenges cfDNA, blocking TLR-mediated pro-inflammatory signaling. Working together with the inherent immunomodulatory functions of MSCs, this dual-action strategy yielded robust efficacy in MRL/lpr mice, including a significant reversal of T-cell dysregulation, restoration of glomerular integrity, and reduction of proteinuria and IgG deposition.Conclusions
We propose that MSC-G3K@T offers a promising route to augment cell-based therapies, creating a versatile platform that could be used to treat autoimmune and inflammatory diseases.
Related
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- Advances in photothermal-driven tumor immunomodulation and synergistic therapy
- Inspiration of Nanoengineered Antimicrobial Therapeutics Against Nontuberculous Mycobacterial Infection.
- Toward precision host-directed immunomodulation in community-acquired pneumonia: a proposed endotype–target–natural-product framework and a roadmap for validation in human lung organoids
BibTeX
@article{tian2026nanoengineered,
title = {{A nanoengineered MSC therapeutic for synergistic therapy of lupus nephritis via cfDNA clearance and targeted immunomodulation.}},
author = {Jiang Tian and Qinyao Xu and Zexin Wang and Zeyu Wang and Haofang Zhu and Lingyun Sun and Zhongwei Gu},
journal = {Theranostics},
year = {2026},
month = sep,
doi = {10.7150/thno.136356},
url = {https://europepmc.org/article/MED/42909248},
note = {CC BY},
}
RIS
TY - JOUR
TI - A nanoengineered MSC therapeutic for synergistic therapy of lupus nephritis via cfDNA clearance and targeted immunomodulation.
AU - Jiang Tian
AU - Qinyao Xu
AU - Zexin Wang
AU - Zeyu Wang
AU - Haofang Zhu
AU - Lingyun Sun
AU - Zhongwei Gu
PY - 2026
DA - 2026/09/03
JO - Theranostics
DO - 10.7150/thno.136356
UR - https://europepmc.org/article/MED/42909248
AB - Rationale Lupus nephritis (LN) remains a clinical challenge due to the dose-limiting toxicity of conventional immunosuppressants and the poor engraftment/efficacy of mesenchymal stromal cell (MSC) therapies.Methods We report a novel nanoengineered MSC therapeutic for LN by engineering MSCs with a cell-free DNA (cfDNA)-targeting dendritic nanogel. To obtain the hybrid MSC-G3K@T system, we coupled tacrolimus-loaded, disulfide-crosslinked polylysine dendrimer nanogels (G3K@T) onto the MSC membrane. Our system exploits two synergistic targeting strategies: the innate homing capacity of MSCs, plus the specific affinity of the cationic G3K dendrimer for anionic cfDNA, which enriches in inflamed kidneys.Results Our system acts through two coordinated actions: the nanogel responds to the oxidative renal microenvironment and releases tacrolimus in a spatiotemporally controlled manner, thereby suppressing T-cell activation. At the same time, it scavenges cfDNA, blocking TLR-mediated pro-inflammatory signaling. Working together with the inherent immunomodulatory functions of MSCs, this dual-action strategy yielded robust efficacy in MRL/lpr mice, including a significant reversal of T-cell dysregulation, restoration of glomerular integrity, and reduction of proteinuria and IgG deposition.Conclusions We propose that MSC-G3K@T offers a promising route to augment cell-based therapies, creating a versatile platform that could be used to treat autoimmune and inflammatory diseases.
SN - 1838-7640
ER -