Multifunctional folate receptor-targeting and pH-responsive nanocarriers loaded with methotrexate for treatment of rheumatoid arthritis

Zhao, Jinlong; Zhao, Menghui; Yu, Changhui; Zhang, Xueyan; Liu, Jiaxin; Cheng, Xinwei; Lee, Robert J.; Sun, Fengying; Teng, Lesheng; Li, Youxin

doi:10.2147/ijn.s140992

Cited by 86 publications

(42 citation statements)

References 39 publications

(30 reference statements)

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“…The result was in the expected line that folate receptor overexpressed macrophages will preferentially internalize the nanoparticle conjugated with folic acid ligand [ 31 ]. The activated macrophages are generally present in the RA and osteoarthritis and cancers and folate-targeted nanoparticle enables the effective accumulation of therapeutics in the diseased site [ 32 ]. Overall, higher internalization in LPS-activated macrophages was attributed to non-opsonic phagocytosis of F-siRML and active targeting of folate receptors.…”

Section: Resultsmentioning

confidence: 99%

Combination of NF-kB targeted siRNA and methotrexate in a hybrid nanocarrier towards the effective treatment in rheumatoid arthritis

Duan

2018

J Nanobiotechnol

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BackgroundThe transcription factor NF-kB plays an important role in the pathogenesis of rheumatoid arthritis (RA). Effective treatment of RA is hindered due to the lack of specificity of small molecules in the inflamed joints. In this study, we aimed to develop a unique hybrid-nanoparticles system comprised of calcium phosphate/liposome to deliver NF-kB-targeted siRNA and methotrexate (MTX) to diseased site.ResultsWe have successfully demonstrated that the combination of siRNA and MTX in a calcium phosphate/liposome-based hybrid nanocarrier could effectively treat the RA. We have showed that folate receptor-targeted nanocarrier system significantly suppression the arthritis progression in mice model. Substantial accumulation of F-siRML was observed in LPS-activated macrophages. These kind of activated macrophages are generally present in the RA and osteoarthritis and folate-targeted nanoparticle enables the effective accumulation of therapeutics in the diseased site. The combinational nanoparticles effectively blocked the NF-kB signaling pathways and reduced the expression of pro-inflammatory cytokines. Furthermore, siRML and F-siRML did not show any decrease in the lymphocyte count indicating that it can avoid the adverse effect of MTX.ConclusionTherefore, siRML and F-siRML provides unique benefits of excellent therapeutic efficacy with excellent safety profile in the arthritic mice and could be an promising approach in the treatment of rheumatoid arthritis.Electronic supplementary materialThe online version of this article (10.1186/s12951-018-0382-x) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Combination of NF-kB targeted siRNA and methotrexate in a hybrid nanocarrier towards the effective treatment in rheumatoid arthritis

Duan

2018

J Nanobiotechnol

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“…Although active targeting modalities such as tuftsin peptides, 120 IL-1Ra, 121 vasoactive intestinal peptides, 122 avb3-targeted RGD, 123,124 folic acid, [125][126][127][128] or macrophagederived microvesicle proteins 129 have been used in various investigations to target cells in the arthritic synovium, there are minimal instances of electrostatic interactions being leveraged for targeting. However, electric charge has been manipulated in other cases to determine preferential targeting of key immune cells that are part of the arthritic synovium, such as phagocytic macrophages.…”

Section: Synoviummentioning

confidence: 99%

Leveraging Electrostatic Interactions for Drug Delivery to the Joint

Kumar

2020

Bioelectricity

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Arthritis is a debilitating joint disease with a high economic burden and prevalence. There are many challenges delivering therapeutics to the joint, including low bioavailability when administered systemically and low joint retention after intra-articular injection. Therefore, drug delivery systems such as nanoparticles, liposomes, dendrimers, and carrier proteins have been utilized to overcome some of these limitations. To enhance joint tissue localization and retention, there are opportunities to leverage electrostatic interactions between drug carriers and various tissues and cells. These opportunities, as they pertain to specific joint tissues, are explored in this review. Further, the impact that electrostatic interactions has on various drug delivery parameters, such as the formation of a protein corona, the uptake and cytotoxicity, and the biodistribution of the drug delivery systems, is discussed. Lastly, this review summarizes key findings from studies that have investigated the use of electrostatic interactions to increase targeting of specific joint tissues and limitations in preclinical investigations are identified. As more novel targets are discovered in treating arthritis, there will be a continued need to localize therapeutics to specific tissues for greater therapeutic outcomes and hence attention must be paid in designing the drug delivery systems.

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“…So far, nanotheranostics has been applied for the treatment of diverse diseases, e.g., cancer, cardiac disease, and rheumatoid arthritis. [303][304][305][306] In particular, GNPs are used to enhance the permeability (up to a desirable level) and retention effect. 307 In theranostics applications, nanoparticles of various sizes and shapes have been used.…”

Section: Nanoscale Advancesmentioning

confidence: 99%