A1 Refereed original research article in a scientific journal
In Vivo Kidney Allograft Endothelial Specific Scavengers for On-Site Inflammation Reduction under Antibody-Mediated Rejection
Authors: Liu Chang, Yan Pengpeng, Xu Xiaoyu, Zhou Wenhui, Prakash Dhayakumar Rajan, Wang Shuqi, Zhou Junnian, Wang Rending, Huang Hongfeng, Chen Jianghua, Zhang Hongbo, Shen Jia
Publisher: WILEY-V C H VERLAG GMBH
Publication year: 2022
Journal: Small
Journal name in source: SMALL
Journal acronym: SMALL
Article number: 2106746
Number of pages: 14
ISSN: 1613-6810
eISSN: 1613-6829
DOI: https://doi.org/10.1002/smll.202106746
Web address : https://onlinelibrary.wiley.com/doi/10.1002/smll.202106746
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/175133446
Kidney transplantation is the most effective therapy for patients with end-stage renal disease. However, antibody-mediated rejection (ABMR) threatens long-term survival of renal grafts. Although ABMR can be controlled by donor-specific antibody clearance and B- or (and) plasma-cells inhibition, the treatment often causes severe side effects in patients. Therefore, there is need to explore site-specific scavengers. In this study, a nanovehicle carrying an anti-inflammatory drug is developed with complement component 4d targeting, a specific biomarker expressed on allograft endothelium under ABMR. Moreover, the nanovehicle is endowed with photothermal properties to control drug release. Analysis through systematic in vitro and in vivo toxicity, non-invasive targeted imaging, and in situ remote controlled drug release show the nanovehicle specifically targets allograft kidney endothelium, releases an anti-inflammatory drug, methylprednisolone, locally upon laser irradiation, and promotes recovery of injured endothelium, without affecting systemic inflammation or innate immune responses. This strategy has the potential for future clinical application in ABMR treatment.
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