Multiplexed PLGA scaffolds with nitric oxide-releasing zinc oxide and melatonin-modulated extracellular vesicles for severe chronic kidney disease

Rhim, Won-Kyu; Woo, Jiwon; Kim, Jun Yong; Lee, Eun Hye; Cha, Seung-Gyu; Kim, Da-Seul; Baek, Seung-Woon; Park, Chun Gwon; Kim, Bum Soo; Kwon, Tae Gyun; Han, Dong Keun

doi:10.1016/j.jare.2024.03.018

Cited by 2 publications

(1 citation statement)

References 69 publications

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“…The AKT is a factor that promotes chondrocyte proliferation and autophagy, which is essential for the maintenance and repair of cartilage [52]. There are numerous studies that indicate that inflammation-inducing factors are ameliorated by EVs, which could contribute to the inflammatory response [53,54]. Apoptosis is a type of "programmed cell death" a natural phenomenon, but it can be triggered by factors such as ROS [55].…”

Section: Bioinformatics Analysis For Estimating Ev Functionalitymentioning

confidence: 99%

Combinatory Nanovesicle with siRNA-Loaded Extracellular Vesicle and IGF-1 for Osteoarthritis Treatments

Kim,

Lee,

Cha

et al. 2024

IJMS

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Extracellular vesicles (EVs) have been found to have the characteristics of their parent cells. Based on the characteristics of these EVs, various studies on disease treatment using mesenchymal stem cell (MSC)-derived EVs with regenerative activity have been actively conducted. The therapeutic nature of MSC-derived EVs has been shown in several studies, but in recent years, there have been many efforts to functionalize EVs to give them more potent therapeutic effects. Strategies for functionalizing EVs include endogenous and exogenous methods. In this study, human umbilical cord MSC (UCMSC)-derived EVs were selected for optimum OA treatments with expectation via bioinformatics analysis based on antibody array. And we created a novel nanovesicle system called the IGF-si-EV, which has the properties of both cartilage regeneration and long-term retention in the lesion site, attaching positively charged insulin-like growth factor-1 (IGF-1) to the surface of the UCMSC-derived Evs carrying siRNA, which inhibits MMP13. The downregulation of inflammation-related cytokine (MMP13, NF-kB, and IL-6) and the upregulation of cartilage-regeneration-related factors (Col2, Acan) were achieved with IGF-si-EV. Moreover, the ability of IGF-si-EV to remain in the lesion site for a long time has been proven through an ex vivo system. Collectively, the final constructed IGF-si-EV can be proposed as an effective OA treatment through its successful MMP13 inhibition, chondroprotective effect, and cartilage adhesion ability. We also believe that this EV-based nanoparticle-manufacturing technology can be applied as a platform technology for various diseases.

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Section: Bioinformatics Analysis For Estimating Ev Functionalitymentioning

confidence: 99%

Combinatory Nanovesicle with siRNA-Loaded Extracellular Vesicle and IGF-1 for Osteoarthritis Treatments

Kim,

Lee,

Cha

et al. 2024

IJMS

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Hybrid Nanoparticle Engineered with Transforming Growth Factor -β1-Overexpressed Extracellular Vesicle and Cartilage-Targeted Anti-Inflammatory Liposome for Osteoarthritis

Kim,

Rhim,

Lee

et al. 2024

ACS Nano

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Extracellular vesicles (EVs) possess the characteristics of their parent cells, based on which various studies have actively investigated treatments for diseases using mesenchymal stem cell-derived EVs due to their regenerative activity. Furthermore, in recent years, there have been significant efforts to engineer EVs to improve their native activities and integrate additional functions. Although both endogenous and exogenous methods are used for engineering EVs, endogenous methods may pose the problem of administering substances to cells undergoing metabolic changes, which can cause potential side effects. In addition, exogenous methods may have the limitation of losing beneficial factors inside EVs due to membrane disruption during engineering processes. Surface modification of EVs may also impair efficiency due to the presence of proteins on the EV surface. Therefore, in this study, a stable and efficient engineering method was achieved through the ethanol-mediated hybridization of EVs and functionalized lipid nanoparticles (LNPs) with a fusogenic lipid component. During hybridization, the internal bioactive factors and targeting moiety were maintained to possess the characteristics of both LNPs and EVs. The Ab-Hybrid, which was successfully synthesized through hybridization with nicotinamide-encapsulated and Col2A1 antibody-modified liposome and Transforming growth factor-β1 (TGF-β1)-overexpressed EVs, was administered to osteoarthritis (OA)-induced rats undergoing the destabilization of the medial meniscus surgery. Ultimately, the Ab-Hybrid demonstrated excellent chondroprotective and anti-inflammatory effects with targeting and long-lasting properties in OA lesions. We anticipate that this approach for manufacturing hybrid particles will serve as a valuable EV engineering method and a versatile platform technology applicable to various diseases.

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Multiplexed PLGA scaffolds with nitric oxide-releasing zinc oxide and melatonin-modulated extracellular vesicles for severe chronic kidney disease

Cited by 2 publications

References 69 publications

Combinatory Nanovesicle with siRNA-Loaded Extracellular Vesicle and IGF-1 for Osteoarthritis Treatments

Combinatory Nanovesicle with siRNA-Loaded Extracellular Vesicle and IGF-1 for Osteoarthritis Treatments

Hybrid Nanoparticle Engineered with Transforming Growth Factor -β1-Overexpressed Extracellular Vesicle and Cartilage-Targeted Anti-Inflammatory Liposome for Osteoarthritis

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