Lymph node targeting of cyclosporine ameliorates ocular manifestations in a mouse model of systemic lupus erythematosus (SLE) via PD-L1.

Autor: Ganugula R; The Center for Convergent Bioscience and Medicine (CCBM), The University of Alabama, Tuscaloosa, AL, USA.; Department of Translational Science and Medicine, College of Community Health Sciences, The University of Alabama, Tuscaloosa, AL, USA.; Alabama Life Research Institute, The University of Alabama, Tuscaloosa, AL, USA.; Department of Biological Sciences, The University of Alabama, Tuscaloosa, AL, USA., Babalola KT; The Center for Convergent Bioscience and Medicine (CCBM), The University of Alabama, Tuscaloosa, AL, USA.; Department of Translational Science and Medicine, College of Community Health Sciences, The University of Alabama, Tuscaloosa, AL, USA.; Alabama Life Research Institute, The University of Alabama, Tuscaloosa, AL, USA., Heyns IM; The Center for Convergent Bioscience and Medicine (CCBM), The University of Alabama, Tuscaloosa, AL, USA.; Department of Translational Science and Medicine, College of Community Health Sciences, The University of Alabama, Tuscaloosa, AL, USA.; Alabama Life Research Institute, The University of Alabama, Tuscaloosa, AL, USA., Arora M; The Center for Convergent Bioscience and Medicine (CCBM), The University of Alabama, Tuscaloosa, AL, USA.; Department of Translational Science and Medicine, College of Community Health Sciences, The University of Alabama, Tuscaloosa, AL, USA.; Alabama Life Research Institute, The University of Alabama, Tuscaloosa, AL, USA.; Department of Biological Sciences, The University of Alabama, Tuscaloosa, AL, USA., Agarwal SK; Section of Immunology, Allergy and Rheumatology, Department of Medicine, Biology of Inflammation Baylor College of Medicine, One Baylor Plaza, Houston, TX, USA., Mohan C; Department of Biomedical Engineering, University of Houston, Houston, TX, USA., Kumar MNVR; The Center for Convergent Bioscience and Medicine (CCBM), The University of Alabama, Tuscaloosa, AL, USA.; Department of Translational Science and Medicine, College of Community Health Sciences, The University of Alabama, Tuscaloosa, AL, USA.; Alabama Life Research Institute, The University of Alabama, Tuscaloosa, AL, USA.; Department of Biological Sciences, The University of Alabama, Tuscaloosa, AL, USA.; Chemical and Biological Engineering, University of Alabama, Tuscaloosa, AL, USA.; Center for Free Radical Biology, University of Alabama at Birmingham, Birmingham, AL, USA.; Nephrology Research and Training Center, Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
Jazyk: angličtina
Zdroj: Nano today [Nano Today] 2024 Aug; Vol. 57. Date of Electronic Publication: 2024 Jun 15.
DOI: 10.1016/j.nantod.2024.102359
Abstrakt: One-third of systemic lupus erythematosus (SLE) patients experience various degrees of ocular manifestations, with immunosuppressants recommended as a treatment option. Targeted immune suppression via oral administration is challenging due to the harsh gastrointestinal tract environment combined with complex physiological barriers. Here, we report the efficacy of orally administered cyclosporine (CsA)-laden polymer nanoparticles decorated with the ligand - Gambogic Acid (P2Ns-GA-CsA) in sustained lymph node delivery. This is the first report demonstrating the CD71 specificity of P2Ns-GA-CsA in the CD71 knockout mouse model and the influence of spacer length in achieving target tissue bioavailability in a lupus mouse model. P2Ns-GA-CsA effectively regulates T-cell chemotaxis by PD-L1 at a 50 % lower dose compared to conventional CsA in a mouse model exhibiting lupus-associated corneal inflammation. Collectively, these results suggest the possibility for further development of P2Ns-GA to target a diverse range of lymphatic disorders.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: R.G. M.A. and M.N.V.R.K. are inventors on patent applications related to the technology described in the manuscript (owned and managed by Texas A&M University, exclusively licensed to Peroral Biosciences, Inc.,). M.N.V.R.K. is a non-paid scientific advisory board member of Peroral Biosciences, Inc., and M.A. is a shareholder of Peroral Biosciences, Inc.
Databáze: MEDLINE
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