Acid-responsive nanoparticles with microneedles for anti‑inflammatory sonodynamic therapy of gouty arthritis.
5 affiliations
- 1College of Mechanical Engineering, Zhejiang University of Technology, Hangzhou, PR China.
- 2Institute of Laser Advanced Manufacturing, Zhejiang University of Technology, Hangzhou, PR China.
- 3College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou, PR China.
- 4Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School, Shanghai, PR China.
- 5Ingénierie des Matériaux Polymères, Université Lyon 1, INSA Lyon, Université Jean Monnet, CNRS, UMR 5223, Villeurbanne, France.
Abstract
The pathological microenvironment of acute gouty arthritis (AGA) features local tissue acidification and the release of a storm of pro-inflammatory cytokines. To address this dual challenge, we engineered an acid-responsive curcumin-loaded nanoparticles microneedle system (Cur-PNPs@MN) that delivers curcumin with pH-triggered release and anti-inflammatory activity. This integrated platform combines a hyaluronic acid (HA)-based dissolving microneedle for localized transdermal delivery of acid-degradable PCADK (poly (cyclohexane-1,4-diyl acetone dimethylene ketal)) curcumin nanoparticles (Cur-PNPs), which are designed for pH-triggered curcumin release at the pathological site. Together, they deliver curcumin, a dual-function agent acting both as an anti-inflammatory compound and a nanoenhanced sonosensitizer. In vitro, the system exhibited acid-responsive drug release and also promoted macrophage uptake, achieving significant curcumin accumulation within 1 hour and saturation by 4 hours. Moreover, it could generate potent ultrasound-induced reactive oxygen species (ROS). The ROS generation capability of Cur-PNPs was 1.47-fold higher than that of Cur‑aggregates, resulting in anapoptosis rate of 29.9% in M1 macrophages. In vivo, the chemo-sonodynamic therapy (Cur-PNPs@MN+Ultrasound (US)) in a rat AGA model significantly alleviated joint swelling and inflammatory infiltration, while drastically suppressing pro-inflammatory cytokines, with IL-1β decreasing from 170.3 to 67.3 pg/mL, TNF-α from 20.8 to 5.9 pg/mL, and IL-6 from 140.9 to 48.2 pg/mL, and achieved therapeutic efficacy comparable to conventional drugs. This work demonstrates a synergistic chemo‑sonodynamic strategy by coupling pH-triggered curcumin release with ultrasound-enhanced ROS generation. This acid-responsive therapeutic strategy enhances anti-inflammatory efficacy and reduction of M1-associated inflammatory responses, offering an effective approach for AGA therapy.
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BibTeX
@article{weng2026acidresponsive,
title = {{Acid-responsive nanoparticles with microneedles for anti‑inflammatory sonodynamic therapy of gouty arthritis.}},
author = {Jiaqi Weng and Lili Feng and Binghui Xie and Linxiao Liu and Shulin Shen and Xuechao Chen and Liting Wang and Yueyue Xie and Jianhua Yao and Laurent David and Qinying Yan},
journal = {Drug delivery},
year = {2026},
month = oct,
doi = {10.1080/10717544.2026.2743337},
url = {https://europepmc.org/article/MED/42868112},
note = {CC BY},
}
RIS
TY - JOUR
TI - Acid-responsive nanoparticles with microneedles for anti‑inflammatory sonodynamic therapy of gouty arthritis.
AU - Jiaqi Weng
AU - Lili Feng
AU - Binghui Xie
AU - Linxiao Liu
AU - Shulin Shen
AU - Xuechao Chen
AU - Liting Wang
AU - Yueyue Xie
AU - Jianhua Yao
AU - Laurent David
AU - Qinying Yan
PY - 2026
DA - 2026/10/13
JO - Drug delivery
DO - 10.1080/10717544.2026.2743337
UR - https://europepmc.org/article/MED/42868112
AB - The pathological microenvironment of acute gouty arthritis (AGA) features local tissue acidification and the release of a storm of pro-inflammatory cytokines. To address this dual challenge, we engineered an acid-responsive curcumin-loaded nanoparticles microneedle system (Cur-PNPs@MN) that delivers curcumin with pH-triggered release and anti-inflammatory activity. This integrated platform combines a hyaluronic acid (HA)-based dissolving microneedle for localized transdermal delivery of acid-degradable PCADK (poly (cyclohexane-1,4-diyl acetone dimethylene ketal)) curcumin nanoparticles (Cur-PNPs), which are designed for pH-triggered curcumin release at the pathological site. Together, they deliver curcumin, a dual-function agent acting both as an anti-inflammatory compound and a nanoenhanced sonosensitizer. In vitro, the system exhibited acid-responsive drug release and also promoted macrophage uptake, achieving significant curcumin accumulation within 1 hour and saturation by 4 hours. Moreover, it could generate potent ultrasound-induced reactive oxygen species (ROS). The ROS generation capability of Cur-PNPs was 1.47-fold higher than that of Cur‑aggregates, resulting in anapoptosis rate of 29.9% in M1 macrophages. In vivo, the chemo-sonodynamic therapy (Cur-PNPs@MN+Ultrasound (US)) in a rat AGA model significantly alleviated joint swelling and inflammatory infiltration, while drastically suppressing pro-inflammatory cytokines, with IL-1β decreasing from 170.3 to 67.3 pg/mL, TNF-α from 20.8 to 5.9 pg/mL, and IL-6 from 140.9 to 48.2 pg/mL, and achieved therapeutic efficacy comparable to conventional drugs. This work demonstrates a synergistic chemo‑sonodynamic strategy by coupling pH-triggered curcumin release with ultrasound-enhanced ROS generation. This acid-responsive therapeutic strategy enhances anti-inflammatory efficacy and reduction of M1-associated inflammatory responses, offering an effective approach for AGA therapy.
SN - 1071-7544
SN - 1521-0464
ER -