Breathing Micelles for Combinatorial Treatment of Rheumatoid Arthritis

Tao, Siyue; Cheng, Jian; Su, Gai; Li, Dan; Shen, Zhiqiang; Tao, Fenghua; You, Tao; Hu, Jinming

doi:10.1002/anie.202010009

Cited by 69 publications

(49 citation statements)

References 42 publications

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“…RA typically features excessive proinflammatory cytokines, for example, interleukin (IL)-1, gradually leading to swollen and impaired joints. [1][2][3][4][5][6] Thus, there is a long-term therapeutic need for patients with RA. Traditionally, steroids or immune-suppressor compounds are employed for the treatment of RA, whereas it is often complicated by medication resistance, poor bioavailability, and a broad range of adverse effects such as osteoporosis, diabetes, and Typically, the nanotherapeutic with ambient particles size of 10-200 nm might effectively facilitate diffusion of the payloads and increase circulation half-life.…”

Section: Introductionmentioning

confidence: 99%

Significantly Improving the Bioefficacy for Rheumatoid Arthritis with Supramolecular Nanoformulations

Zhang

et al. 2021

Advanced Materials

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liver function abnormalities. [7,8] Recently there is accumulating research interests focused on treat-to-target approaches against RA, including active interference of IL-1 pathway and other selective strategies. [9][10][11][12][13] Particularly, the treatment of blocking IL-1 is regarded as an effective targeted therapy for IL-1-directed inflammatory diseases, in contrast to attenuated performance of the non-specific antiinflammatory drugs. [13] Although the medication of IL-1 receptor antagonist (IL1ra) has been approved by the US Food and Drug Administration (FDA), it is reported that the protein IL1ra therapeutic and derivatives show short half-life from a few minutes to 1-4 h. [14][15][16] It therefore requires frequent dosage administration as high as 1-2 times per day, which greatly decreases patient compliance and results in higher expenses. [13,17] Thus, there is still largely unmet clinical need to prolong systemic circulation of the medication and increase bioavailability to realize long-acting effect and increase the drug regimen.Nanoparticle-based therapy has attracted tremendous attention in arthritis and related-biomedical communities over past few years. [18][19][20][21][22][23] Owing to its effective approach which provides protection of encapsulated payloads from degradation in the circulation, the formulation of drugs into nanoparticles has many potential advantages over conventional modalities especially in enhanced bioavailability and improved efficacy. [24,25] As a typical inflammatory disease with chronic pain syndromes, rheumatoid arthritis (RA) generally requires long-term treatment with frequent injection administration at 1-2 times per day, because common medications such as interleukin1 receptor antagonist (IL1ra) have poor bioavailability and very limited half-life residence. Here a novel strategy to fabricate nanotherapeutic formulations employing genetically engineered IL1ra protein complexes, yielding ultralong-lasting bioefficacy is developed rationally. Using rat models, it is shown that these nanotherapeutics significantly improved drug regimen to a single subcutaneous administration in a 14-day therapy, suggesting their extraordinary bioavailability and ultralong-acting pharmacokinetics. Specifically, the half-life and bioavailability of the nanoformulations are boosted to the level of 30 h and by 7 times, respectively, significantly greater than other systems. This new strategy thus holds great promise to potently improve patient compliance in RA therapy, and it can be adapted for other therapies that suffer similar drawbacks.

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Section: Introductionmentioning

confidence: 99%

Significantly Improving the Bioefficacy for Rheumatoid Arthritis with Supramolecular Nanoformulations

Zhang

et al. 2021

Advanced Materials

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“…have designed NO‐inhale and carbon monoxide (CO)‐exhale micelles, referred to as breathing micelles (BMs), for synergistic antioxidant therapy in rheumatoid arthritis. [ 182 ] Visible light‐responsive and metal‐free CO donors and OPD moieties were conjugated with PEG backbone for “inhaling NO” and “exhaling CO,” respectively, and self‐assembled to formulate polymeric micelles scavenging NO and releasing CO. The BMs reduced NO and proinflammatory cytokine levels in the LPS‐induced inflammatory environment.…”

Section: Polymer‐based Delivery Of Antioxidantsmentioning

confidence: 99%

Polymeric Antioxidant Materials for Treatment of Inflammatory Disorders

Yeo

Lee

et al. 2021

Advanced Therapeutics

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Reactive oxygen and nitrogen species (RONS) play a key role in physiological conditions as signaling molecules for regulating homeostasis in the human body. However, abnormally increased RONS levels can damage DNA, protein, and tissue, or even impair cellular signaling. Consequently, when this state is present for a long time, it can lead to severe inflammatory disorders, such as lupus, diabetes, rheumatoid arthritis, Crohn's disease, and neurodegenerative disorders. Although antioxidant therapies have been developed for a long time to treat acute or chronic inflammatory diseases, small molecule‐based antioxidants showed relatively low therapeutic effects due to rapid clearance and low stability in the bloodstream. As one of the solutions to overcome such limitations, incorporating polymers would provide enhanced blood stability, bioavailability, and even enhanced therapeutic effects. Herein, diverse polymeric antioxidant materials are introduced that are categorized into simple loading strategies and polymers with inherent antioxidative activity. Further, preclinical and clinical studies of polymeric antioxidant materials for anti‐inflammatory therapy are discussed and a better direction is provided for these to be pursued and improved in anti‐inflammatory therapy.

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“…11, 12 While high levels of ROS and NO induce polarization of macrophages to the M1 subtype, the scavenging of ROS/NO can switch M1 macrophages into M2 macrophages and therefore represents an alternative strategy for RA treatment. 13 Though a number of nanodrugs (e.g. manganese ferrite/ceria nanoparticle, 14 silver nanoparticle 15 and NO-scavenging hydrogel 16, 17 ) that can either eliminate ROS or NO have been developed to treat RA, there is still deficiency of nanomedicines with fully predictable structures, minima off-target toxicity, long duration and stability.…”

Section: Introductionmentioning

confidence: 99%

DNA origami as a nanomedicine for targeted rheumatoid arthritis therapy through reactive oxygen species and nitric oxide scavenging

Shi

et al. 2022

Preprint

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High levels of reactive oxygen species (ROS) and nitric oxide (NO) generated by M1 macrophages induce inflammation in the development of rheumatoid arthritis (RA). The eliminating of ROS and NO therefore represents an alternative strategy for RA treatment. Because DNA molecules possess ROS- and endogenous NO-scavenging capability, herein, we develop a nanomedicine based on triangular DNA origami nanostructures for targeted RA treatment. We showed that folic acid-modified triangular DNA origami nanostructures (FA-tDONs) could reduce ROS and NO simultaneously inside proinflammatory M1 macrophages, leading to their polarization into anti-inflammatory M2 subtype. Further in vivo studies confirmed that FA-tDONs could actively target inflamed joints in collagen-induced arthritis (CIA) mice, attenuate inflammatory cytokines and alleviate disease progression. This work demonstrated that DNA origami itself could act as a potential nanomedicine for targeted RA treatment.

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Breathing Micelles for Combinatorial Treatment of Rheumatoid Arthritis

Cited by 69 publications

References 42 publications

Significantly Improving the Bioefficacy for Rheumatoid Arthritis with Supramolecular Nanoformulations

Significantly Improving the Bioefficacy for Rheumatoid Arthritis with Supramolecular Nanoformulations

Polymeric Antioxidant Materials for Treatment of Inflammatory Disorders

DNA origami as a nanomedicine for targeted rheumatoid arthritis therapy through reactive oxygen species and nitric oxide scavenging

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