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Viral Mimicking Polyplexes as Hierarchical Unpacking Vectors for Rheumatoid Arthritis Treatment.

ABSTRACT: Nano-delivery systems hold great promise for the treatment of rheumatoid arthritis (RA). Current research efforts are primarily focused on enhancing their targeting capabilities and efficacy. Here, this study proposes a novel viral-mimicking ternary polyplexes system for the controlled delivery of the anti-inflammatory drug Cyclosporin A (CsA) to effectively treat RA. The ternary polyplexes consist of a nanogel core loaded with CsA and a hyaluronic acid shell, which facilitates CD44-mediated targeting. By mimicking the Trojan Horse strategy employed by viruses, these polyplexes undergo a stepwise process of deshielding and disintegration within the inflamed joints. This process leads to the release of CsA within the cells and the scavenging of pathogenic factors. This study demonstrates that these viral-mimicking ternary polyplexes exhibit rapid targeting, high accumulation, and prolonged persistence in the joints of RA mice. As a result, they effectively reduce inflammation and alleviate symptoms. These results highlight the potential of viral-mimicking ternary polyplexes as a promising therapeutic approach for the targeted and programmed delivery of drugs to treat not only RA but also other autoimmune diseases.

SUBMITTER: Zhu H

PROVIDER: S-EPMC11348054 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature

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Viral Mimicking Polyplexes as Hierarchical Unpacking Vectors for Rheumatoid Arthritis Treatment.

Zhu Haofang H Huang Danqing D Wang Jinglin J Zhao Yuanjin Y Sun Lingyun L

Advanced science (Weinheim, Baden-Wurttemberg, Germany) 20240625 32

Nano-delivery systems hold great promise for the treatment of rheumatoid arthritis (RA). Current research efforts are primarily focused on enhancing their targeting capabilities and efficacy. Here, this study proposes a novel viral-mimicking ternary polyplexes system for the controlled delivery of the anti-inflammatory drug Cyclosporin A (CsA) to effectively treat RA. The ternary polyplexes consist of a nanogel core loaded with CsA and a hyaluronic acid shell, which facilitates CD44-mediated tar ...[more]

PMID: 38923874

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Project description:In 15 patients with rheumatoid arthritis the baseline expression (t=0) of type I IFN-regulated genes was determined in peripheral blood cells (PAXgene) using cDNA-microarrays and compared to levels one month after (t=1) anti-TNF treatment (infliximab). Therefore, we used 43K cDNA microarrays from the Stanford Functional Genomics Facility (http://microarray.org/sfgf/) printed on aminosilane-coated slides containing ~20.000 unique genes. Only one batch of arrays was used for all experiments. First DNA spots were UV-cross linked to the slide using 150-300 mJoules. Sample preparation and microarray hybridization were performed as described previously (1,2). Data storage and filtering was performed using the Stanford Microarray Database (http://genome-www5.stanford.edu//) as described previously. 1. van der Pouw Kraan TC, Wijbrandts CA, van Baarsen LG, Voskuyl AE, Rustenburg F, Baggen JM et al.: Rheumatoid arthritis subtypes identified by genomic profiling of peripheral blood cells: assignment of a type I interferon signature in a subpopulation of patients. Ann Rheum Dis 2007, 66: 1008-1014. 2. van der Pouw Kraan TC, van Baarsen LG, Rustenburg F, Baltus B, Fero M, Verweij CL: Gene expression profiling in rheumatology. Methods Mol Med 2007, 136: 305-327. Abbreviations: - Bnrs are the different patients analyzed - PAX or Paxgene indicates the total RNA was isolated from peripheral blood obtained in PAXgene tubes - CRS: common reference sample: We made a common reference that consisted of a mixture of mRNAs isolated from 11 different cell lines (Perou CM, Jeffrey SS, van de RM et al. Distinctive gene expression patterns in human mammary epithelial cells and breast cancers. Proc Natl Acad Sci U S A. 1999; 96:9212-9217) supplemented with RNA from rheumatoid synovial tissue, fibroblasts, and activated peripheral blood mononuclear cells (PBMCs). - PMT: photomultiplier tube: the sensitivity/intensity of the scanner can be adjusted to prevent spot saturation. Compound Based Treatment: anti-TNF (infliximab)

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Viral Mimicking Polyplexes as Hierarchical Unpacking Vectors for Rheumatoid Arthritis Treatment.

Publications

Viral Mimicking Polyplexes as Hierarchical Unpacking Vectors for Rheumatoid Arthritis Treatment.

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