Abstract
Our previous study showed that the functionalized E-selectin targeted MBs (TMB-E−selectin) may become a novel drug delivery vector for inflammatory diseases. Therefore, the purpose of this study was to investigate the effect of TMB-E−selectin and methylprednisolone (MP) co-administration combined with ultrasound (US) on cisplatin-induced acute kidney injury (AKI) in rats. After modeling with a single intraperitoneal injection of 10 mg/kg of cisplatin, the rats were intravenously administered with MP or TMB-E−selectin alone, or their mixtures. US was immediately applied for 10 min on bilateral kidneys in rats with TMB-E−selectin treatment. Results showed that 50 mg/kg MP alone and the mixture of 20 mg/kg MP and 500 µL/kg TMB-E−selectin combined with US significantly reduced the levels of BUN and Scr, renal injuries, and the expressions of E-selectin, IL-1α, TNF-α, and NF-κB in renal tissues, but these therapy effects were not significantly observed by 20 mg/kg MP alone. In conclusion, TMB-E−selectin combined with US can enhance the anti-inflammatory and renoprotective effects of the MP in rats with AKI then decrease systemic required dosage and improve the bioavailability of glucocorticoids, which mechanism mainly associates with local drug delivery mediated by US targeted microbubbles cavitation.
Data availability
The data for this study findings are available within the article.
References
Fung, A. T. et al. Local delivery of corticosteroids in clinical ophthalmology: A review. Clin. Exp. Ophthalmol. 48, 366–401. https://doi.org/10.1111/ceo.13702 (2020).
Fournier, L., de La Taille, T. & Chauvierre, C. Microbubbles for human diagnosis and therapy. Biomaterials 294, 122025. https://doi.org/10.1016/j.biomaterials.2023.122025 (2023).
Li, H. et al. Highlights in ultrasound-targeted microbubble destruction-mediated gene/drug delivery strategy for treatment of malignancies. Int. J. Pharm. 613, 121412. https://doi.org/10.1016/j.ijpharm.2021.121412 (2022).
He, Y. et al. Reversible opening of the blood-labyrinth barrier by low-pressure pulsed ultrasound and microbubbles for the treatment of inner ear diseases. J. Control Release. 372, 318–330. https://doi.org/10.1016/j.jconrel.2024.06.043 (2024).
Mehta, R. I. et al. Ultrasound-mediated blood-brain barrier opening uncovers an intracerebral perivenous fluid network in persons with Alzheimer’s disease. Fluids Barriers CNS. 20, 46. https://doi.org/10.1186/s12987-023-00447-y (2023).
Wang, L. et al. Ultrasound-targeted microbubble destruction augmented synergistic therapy of rheumatoid arthritis via targeted liposomes. J. Mater. Chem. B. 8, 5245–5256. https://doi.org/10.1039/d0tb00430h (2020).
Sharma, D. & Czarnota, G. J. Using ultrasound and microbubble to enhance the effects of conventional cancer therapies in clinical settings. Cancer Metastasis Rev. 44, 39. https://doi.org/10.1007/s10555-025-10255-5 (2025).
Yang, S., Zhang, R., Zhang, H. & Lu, Y. Ultrasound-targeted microbubble destruction: a prospective strategy for treating cardiovascular disease. Front. Cardiovasc. Med. 12, 1634059. https://doi.org/10.3389/fcvm.2025.1634059 (2025).
Wang, Y. et al. Advances in ultrasound-mediated brain drug delivery. J. Pharm. Pharmacol. https://doi.org/10.1093/jpp/rgaf090 (2025).
Si, R. et al. A novel lipid microbubble targeting E-selectin for ultrasound molecular imaging of acute kidney injury in rats. Mol. Pharm. 22, 6163–6173. https://doi.org/10.1021/acs.molpharmaceut.5c00883 (2025).
Yang, Y. et al. Renoprotective approaches and strategies in acute kidney injury. Pharmacol. Ther. 163, 58–73. https://doi.org/10.1016/j.pharmthera.2016.03.015 (2016).
Perse, M. & Veceric-Haler, Z. Cisplatin-induced rodent model of kidney injury: Characteristics and challenges. Biomed. Res. Int. 1462802, https://doi.org/10.1155/2018/1462802 (2018).
Liu, D. et al. A practical guide to the monitoring and management of the complications of systemic corticosteroid therapy. Allergy Asthma Clin. Immunol. 9 https://doi.org/10.1186/1710-1492-9-30 (2013).
Yang, H. et al. The effects of ultrasound-targeted microbubble destruction (UTMD) carrying IL-8 monoclonal antibody on the inflammatory responses and stability of atherosclerotic plaques. Biomed. Pharmacother. 118, 109161. https://doi.org/10.1016/j.biopha.2019.109161 (2019).
Bae, Y. J., Yoon, Y. I., Yoon, T. J. & Lee, H. J. Ultrasound-guided delivery of siRNA and a chemotherapeutic drug by using microbubble complexes: In vitro and in vivo evaluations in a prostate cancer model. Korean J. Radiol. 17, 497–508. https://doi.org/10.3348/kjr.2016.17.4.497 (2016).
Hong, D., Yang, J., Guo, J., Zhang, Y. & Chen, Z. Ultrasound-targeted microbubble destruction enhances inhibitory effect of Apatinib on angiogenesis in Triple negative breast carcinoma xenografts. Anal. Cell. Pathol. (Amst). 2021 8837950, (2021).
Jiang, X. et al. A review of low-intensity pulsed ultrasound for therapeutic applications. IEEE Trans. Biomed. Eng. 66, 2704–2718. https://doi.org/10.1109/TBME.2018.2889669 (2019).
Engelmann, J. et al. Pulsed ultrasound and dimethylsulfoxide gel treatment reduces the expression of pro-inflammatory molecules in an animal model of muscle injury. Ultrasound Med. Biol. 38, 1470–1475. https://doi.org/10.1016/j.ultrasmedbio.2012.03.020 (2012).
Nakamura, T. et al. Low-intensity pulsed ultrasound reduces the inflammatory activity of synovitis. Ann. Biomed. Eng. 39, 2964–2971. https://doi.org/10.1007/s10439-011-0408-0 (2011).
Crossman, J. et al. Low intensity pulsed ultrasound increases mandibular height and Col-II and VEGF expression in arthritic mice. Arch. Oral Biol. 104, 112–118. https://doi.org/10.1016/j.archoralbio.2019.05.032 (2019).
Song, W. S. et al. Neuroprotection by abdominal ultrasound in lipopolysaccharide-induced systemic inflammation. Int. J. Mol. Sci. 24 https://doi.org/10.3390/ijms24119329 (2023).
Fu, S. et al. Protective effect of low-intensity pulsed ultrasound on immune checkpoint inhibitor-related myocarditis via fine-tuning CD4(+) T-cell differentiation. Cancer Immunol. Immunother. 73, 15. https://doi.org/10.1007/s00262-023-03590-5 (2024).
Aibara, Y. et al. Daily low-intensity pulsed ultrasound ameliorates renal fibrosis and inflammation in experimental hypertensive and diabetic nephropathy. Hypertension 76, 1906–1914. https://doi.org/10.1161/HYPERTENSIONAHA.120.15237 (2020).
Liang, W. et al. Low-intensity pulsed ultrasound: A physical stimulus with immunomodulatory and anti-inflammatory potential. Ann. Biomed. Eng. 52, 1955–1981. https://doi.org/10.1007/s10439-024-03523-y (2024).
Yang, T., Liang, C., Chen, L., Li, J. & Geng, W. Low-intensity pulsed ultrasound alleviates hypoxia-induced chondrocyte damage in temporomandibular disorders by modulating the hypoxia-inducible factor pathway. Front. Pharmacol. 11, 689. https://doi.org/10.3389/fphar.2020.00689 (2020).
Cao, Q. et al. Low-intensity pulsed ultrasound of different intensities differently affects myocardial ischemia/reperfusion injury by modulating cardiac oxidative stress and inflammatory reaction. Front. Immunol. 14, 1248056. https://doi.org/10.3389/fimmu.2023.1248056 (2023).
Huang, P. et al. Enhanced antitumor efficacy of ultrasonic cavitation with up-sized microbubbles in pancreatic cancer. Oncotarget 6, 20241–20251. https://doi.org/10.18632/oncotarget.4048 (2015).
Acknowledgements
The authors thank professor Yili Wang and Liang Bai for help with qRT-PCR. This work was funded by the National Natural Science Foundation of China (grant number 82070792).
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All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Ruoyan Si, Liping Mo, Changan Zhao, Zeyu Xu, Wenbao Zhao, Junfeng Wu, Rongguo Fu and Shuting Ren. The first draft of the manuscript was written by Ruoyan Si and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
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Si, R., Mo, L., Zhao, C. et al. E-selectin-targeted microbubbles combined with ultrasound improves renoprotective effects of methylprednisolone on cisplatin-induced acute kidney injury in rats. Sci Rep (2026). https://doi.org/10.1038/s41598-026-47547-x
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DOI: https://doi.org/10.1038/s41598-026-47547-x
