To investigate the effect of carrier-free self-assembled berberine-curcumin nanoparticles （Ber-Cur NPs） on chronic wound healing in rats.

Ber-Cur NPs were prepared using the antisolvent precipitation method. The physicochemical characteristics of Ber-Cur NPs were evaluated by scanning electron microscopy，transmission electron microscopy，energy-dispersive spectroscopy，dynamic light scattering，Fourier transform infrared spectroscopy，and confocal laser scanning microscopy. The in vitro antioxidant activity of Ber-Cur NPs were assessed using 2，2'-azino-bis （3-ethylbenzothiazoline-6-sulfonic acid） （ABTS），1，1-diphenyl-2-picrylhydrazyl （DPPH），and 2-phenyl-4，4，5，5-tetramethylimidazoline-1-oxyl 3-oxide （PTIO） free radical scavenging assays. Intracellular reactive oxygen species （ROS） scavenging ability was detected using the 2'，7'-dichlorodihydrofluorescein diacetate （DCFH-DA） fluorescent probe. Cell compatibility and the protective effect of Ber-Cur NPs against hydrogen peroxide （H₂O₂） -induced oxidative stress injury were evaluated using the methyl thiazolyl tetrazolium （MTT） assay. Twenty-five Sprague-Dawley rats were established chronic wound models on the back and were randomly divided into the control group，model group，and low，medium，and high dose Ber-Cur NPs groups. Wounds in each group were treated with daily dressing changes. The control and model groups received normal saline，while the low，medium，and high dose Ber-Cur NPs groups received 0.1，0.5，and 2.0 mg/mL Ber-Cur NPs，respectively. Wound images were obtained on days 7 and 15 after treatment，and the wound healing rate was calculated. On day 15 after treatment，wound tissues were collected to determine superoxide dismutase （SOD） activity and malondialdehyde （MDA） levels. Interleukin-6 （IL-6） expression was detected by immunohistochemistry，and CD31 expression was detected by immunofluorescence staining. The biosafety of Ber-Cur NPs were evaluated using the MTT assay，hematoxylin and eosin （HE） staining of major organs，and hematological analysis.

Ber-Cur NPs exhibited a quasi-spherical morphology，with a particle size of （44.25±11.73） nm，a hydration particle size of 108.10 nm，and a zeta potential of +7.6 mV. Fourier-transform infrared spectroscopy indicated that hydrogen bonding，π-π stacking，and electrostatic interactions between Ber and Cur may jointly drive the self-assembly process. Dual-channel fluorescence localization showed a high degree of overlap between the fluorescence signals of Ber and Cur in the nanoparticles，suggesting that both components participated in the formation of the self-assembled nanoparticles. In vitro experiments showed that Ber-Cur NPs had favorable scavenging effects on ABTS，DPPH，and PTIO free radicals，as well as intracellular ROS，and improved the survival rate of cells subjected to oxidative stress injury. MTT results showed that the cell survival rates of Ber-Cur NPs treatment were above 80% within the concentration range of 0–200 μg/mL. After high dose Ber-Cur NPs treatment，no significant abnormalities were observed on the liver and kidney function indicators or the HE staining of major organs in the rats. Compared with the model group，Ber-Cur NPs treatment increased the wound healing rate，enhanced SOD activity and CD31 expression，and reduced MDA level and IL-6 expression in wound tissues.

Ber-Cur NPs can improve chronic wound healing in rats by reducing oxidative stress，inhibiting inflammatory responses，and promoting angiogenesis.