Metformin Nanodelivery System Alleviates Morphine-Induced Analgesic Tolerance via Inhibiting the TXNIP/NLRP3/GSDMD Axis

Dandan Yao; Xintong Zhao; Yi Wang; Xiaohai Xu; Liang Cao; Tingting Sun; Ayang Zhao; Jing Chen

doi:10.1021/acsabm.5c01748

Metformin Nanodelivery System Alleviates Morphine-Induced Analgesic Tolerance via Inhibiting the TXNIP/NLRP3/GSDMD Axis

Dandan Yao
, Xintong Zhao
, Yi Wang
, Xiaohai Xu
, Liang Cao
, Tingting Sun
, Ayang Zhao^*
, Jing Chen^*

^*Corresponding author for this work

Harbin Medical University
Yantai Yuhuangding Hospital
Chinese Academy of Medical Sciences
School of Medicine and Health, Harbin Institute of Technology

Research output: Contribution to journal › Article › peer-review

Abstract

Morphine-induced analgesic tolerance limits its clinical use. This study shows that metformin alleviates such tolerance by inhibiting the TXNIP/NLRP3/GSDMD axis, reducing microglial activation and proinflammatory cytokines in CD-1 mice (metformin 200 mg/kg i.p.; morphine 10 mg/kg s.c.) and BV-2 cells (metformin 100 μM; morphine 200 μM). TXNIP is critical, as its overexpression weakens metformin’s effect. The TXNIP siRNA/metformin coloaded TM@ZIF-8/HA nanosystem enhances efficacy via pH-responsive, CD44-targeted delivery with good biocompatibility, providing a perioperative pain management strategy.

Original language	English
Pages (from-to)	11075-11088
Number of pages	14
Journal	ACS Applied Bio Materials
Volume	8
Issue number	12
DOIs	https://doi.org/10.1021/acsabm.5c01748
State	Published - 15 Dec 2025
Externally published	Yes

Keywords

TXNIP/NLRP3/GSDMD
metformin
microglia
morphine tolerance
nanodelivery

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10.1021/acsabm.5c01748

Cite this

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title = "Metformin Nanodelivery System Alleviates Morphine-Induced Analgesic Tolerance via Inhibiting the TXNIP/NLRP3/GSDMD Axis",

abstract = "Morphine-induced analgesic tolerance limits its clinical use. This study shows that metformin alleviates such tolerance by inhibiting the TXNIP/NLRP3/GSDMD axis, reducing microglial activation and proinflammatory cytokines in CD-1 mice (metformin 200 mg/kg i.p.; morphine 10 mg/kg s.c.) and BV-2 cells (metformin 100 μM; morphine 200 μM). TXNIP is critical, as its overexpression weakens metformin{\textquoteright}s effect. The TXNIP siRNA/metformin coloaded TM@ZIF-8/HA nanosystem enhances efficacy via pH-responsive, CD44-targeted delivery with good biocompatibility, providing a perioperative pain management strategy.",

keywords = "TXNIP/NLRP3/GSDMD, metformin, microglia, morphine tolerance, nanodelivery",

author = "Dandan Yao and Xintong Zhao and Yi Wang and Xiaohai Xu and Liang Cao and Tingting Sun and Ayang Zhao and Jing Chen",

note = "Publisher Copyright: {\textcopyright} 2025 American Chemical Society.",

year = "2025",

month = dec,

day = "15",

doi = "10.1021/acsabm.5c01748",

language = "英语",

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AU - Yao, Dandan

AU - Zhao, Xintong

AU - Wang, Yi

AU - Xu, Xiaohai

AU - Cao, Liang

AU - Sun, Tingting

AU - Zhao, Ayang

AU - Chen, Jing

PY - 2025/12/15

Y1 - 2025/12/15

N2 - Morphine-induced analgesic tolerance limits its clinical use. This study shows that metformin alleviates such tolerance by inhibiting the TXNIP/NLRP3/GSDMD axis, reducing microglial activation and proinflammatory cytokines in CD-1 mice (metformin 200 mg/kg i.p.; morphine 10 mg/kg s.c.) and BV-2 cells (metformin 100 μM; morphine 200 μM). TXNIP is critical, as its overexpression weakens metformin’s effect. The TXNIP siRNA/metformin coloaded TM@ZIF-8/HA nanosystem enhances efficacy via pH-responsive, CD44-targeted delivery with good biocompatibility, providing a perioperative pain management strategy.

AB - Morphine-induced analgesic tolerance limits its clinical use. This study shows that metformin alleviates such tolerance by inhibiting the TXNIP/NLRP3/GSDMD axis, reducing microglial activation and proinflammatory cytokines in CD-1 mice (metformin 200 mg/kg i.p.; morphine 10 mg/kg s.c.) and BV-2 cells (metformin 100 μM; morphine 200 μM). TXNIP is critical, as its overexpression weakens metformin’s effect. The TXNIP siRNA/metformin coloaded TM@ZIF-8/HA nanosystem enhances efficacy via pH-responsive, CD44-targeted delivery with good biocompatibility, providing a perioperative pain management strategy.

KW - TXNIP/NLRP3/GSDMD

KW - metformin

KW - microglia

KW - morphine tolerance

KW - nanodelivery

UR - https://www.scopus.com/pages/publications/105025058497

U2 - 10.1021/acsabm.5c01748

DO - 10.1021/acsabm.5c01748

M3 - 文章

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ER -

Metformin Nanodelivery System Alleviates Morphine-Induced Analgesic Tolerance via Inhibiting the TXNIP/NLRP3/GSDMD Axis

Abstract

Keywords

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