ArticleJournal of controlled release : official journal of the Controlled Release Society2013
A rapamycin-binding protein polymer nanoparticle shows potent therapeutic activity in suppressing autoimmune dacryoadenitis in a mouse model of Sjögren's syndrome.
Article in Journal of controlled release : official journal of the Controlled Release Society, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
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Who cites it
69 citing papers in PubMed, 108 citations in OpenAlex.
- Pathological mechanisms of Sjögren's disease-related dry eye: from multiglandular dysfunction to ocular surface inflammation.International ophthalmology · 2026Review
- Intracellular GRP78-Directed Delivery of Rapamycin by Biomolecular Condensates of Hydra-Elastin-like Polypeptides.Biomacromolecules · 2026Article
- Advances in nanotechnology for the diagnosis and management of autoimmune diseases.Asian journal of pharmaceutical sciences · 2026Review
- mTOR signaling pathway in primary Sjögren's syndrome: Pathogenesis and potential therapeutic targets (Review).International journal of molecular medicine · 2026Review
- Bioinspired membrane-fusogenic nanomicelles for synergistic chemotherapy, photodynamic therapy, and gas therapy of breast cancer.Materials today. Bio · 2026Article
- Targeted paclitaxel delivery in ovarian cancer via AP1-functionalized elastin-like polypeptide nanocarriers: development and characterization.BMC cancer · 2026Article
- Nanotechnology-Based Modulation of Autoimmune Microenvironments in Sjögren's Syndrome: A Review of Mechanistic Perspectives.International journal of nanomedicine · 2026Review
- Rational design and preclinical evaluation of elastin-like polypeptide micelle nanoparticles for drug delivery.Frontiers in bioengineering and biotechnology · 2026Review
- Rapamycin nanoparticles suppress autoreactive lymphocytes and reduce anti-mitochondrial antibodies in primary biliary cholangitis: Mechanisms and implications.World journal of hepatology · 2025Article
- Immune cell senescence in autoimmunity: implications for disease pathogenesis and therapeutic targeting.Frontiers in immunology · 2025Review
- Causal Relationship Between Sjögren's Syndrome and Gut Microbiota: A Two-Sample Mendelian Randomization Study.Biomedicines · 2024Article
- Redox Pathogenesis in Rheumatic Diseases.ACR open rheumatology · 2024Review
- Research progress of ophthalmic preparations of immunosuppressants.Drug delivery · 2023Review
- Combined therapy of prednisone and mTOR inhibitor sirolimus for treating retroperitoneal fibrosis.Annals of the rheumatic diseases · 2023Article
- Engineered Extracellular Vesicles in Treatment of Type 1 Diabetes Mellitus: A Prospective Review.Biomedicines · 2022Review
- Immune modulating nanoparticles for the treatment of ocular diseases.Journal of nanobiotechnology · 2022Review
- Advances in regenerative medicine applications of tetrahedral framework nucleic acid-based nanomaterials: an expert consensus recommendation.International journal of oral science · 2022Review
- Protein and polypeptide mediated delivery to the eye.Advanced drug delivery reviews · 2022Review
- Hydra-Elastin-like Polypeptides Increase Rapamycin Potency When Targeting Cell Surface GRP78.Biomacromolecules · 2022Article
- Involvement of MST1/mTORC1/STAT1 activity in the regulation of B-cell receptor signalling by chemokine receptor 2.Clinical and translational medicine · 2022Article
9 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Sjögren's syndrome (SjS) is a chronic autoimmune disease characterized initially by lymphocytic infiltration and destruction of exocrine glands, followed by systemic organ damage and B-cell lymphoma. Conventional treatment is based on management of symptoms and there is a shortage of therapies that address the underlying causes of inflammation at source exocrine tissue. The aim of this study was to test a novel protein polymer-based platform consisting of diblock copolymers composed from Elastin-like Polypeptides (ELPs) fused with FKBP12, to deliver a potent immunosuppressant with dose-limiting toxicity, rapamycin (Rapa) also known as Sirolimus, and evaluate its effects on the inflamed lacrimal gland (LG) of non-obese diabetic mouse (NOD), a classic mouse model of SjS. Both soluble and diblock copolymer ELPs were fused to FKBP12 and characterized with respect to purity, hydrodynamic radii, drug entrapment and release. Both formulations showed successful association with Rapa; however, the nanoparticle formulation, FSI, released drug with nearly a 5 fold longer terminal half-life of 62.5h. The strong interaction of FSI nanoparticles with Rapa was confirmed in vivo by a shift in the monoexponential pharmacokinetic profile for free drug to a biexponential profile for the nanoparticle formulation. When acutely administered by injection into NOD mice via the tail vein, this FSI formulation significantly suppressed lymphocytic infiltration in the LG relative to the control group while reducing toxicity. There was also a significant effect on inflammatory and mammalian target of Rapamycin (mTOR) pathway genes in the LG and surprisingly, our nanoparticle formulation was significantly better at decreasing a proposed tear biomarker of SjS, cathepsin S (CATS) compared to free drug. These findings suggest that FSI is a promising tool for delivering Rapa for treatment of SjS in a murine model and may be further explored to meet the unmet medical challenge of SjS.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.