Targeted inhibition of SIRT6 via engineered exosomes impairs tumorigenesis and metastasis in prostate cancer

Han, Qing; Xie, Charles; Fan, Li; Cheng, Yirui; Wu, Tingyu; Zhang, Yanshuang; Lu, Xiaoxuan; Wong, Anson; Sha, Jianjun; Xia, Weiliang

doi:10.7150/thno.53886

Cited by 66 publications

(41 citation statements)

References 53 publications

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“…The use of engineered strategies to improve EVs has been extensively studied in the field of oncology (such as prostate cancer [ 80 ], breast cancer [ 81 ]) and rheumatoid arthritis [ 82 ]. The strategy has gradually received attention in the treatment of OA/cartilage injury.…”

Section: Engineered Ev Strategymentioning

confidence: 99%

The Role of Extracellular Vesicles in the Pathogenesis, Diagnosis, and Treatment of Osteoarthritis

2021

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Osteoarthritis (OA) is a degenerative joint disease that affects the entire joint and has been a tremendous burden on the health care system worldwide. Although cell therapy has made significant progress in the treatment of OA and cartilage regeneration, there are still a series of problems. Recently, more and more evidence shows that extracellular vesicles (EVs) play an important role in the progression and treatment of OA. Here, we discuss that EVs from different cell sources not only participate in OA progression, but can also be used as effective tools for the diagnosis and treatment of OA. In addition, cell pretreatment strategies and EV tissue engineering play an increasingly prominent role in the field of OA treatment. This article will systematically review the latest developments in these areas. As stated above, it may provide new insights for improving OA and cartilage regeneration.

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Section: Engineered Ev Strategymentioning

confidence: 99%

The Role of Extracellular Vesicles in the Pathogenesis, Diagnosis, and Treatment of Osteoarthritis

2021

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“… 33 Multiple studies have reported successful utilization of electroporation as a technique to load siRNAs into sEVs and downregulate the expression of specific targets. 32 , 34 , 40 , 54 A few studies have also reported that electroporation can induce aggregation and at high voltages cause damage of EVs. 46 , 47 Our NTA data show a comparable pre- and post-electroporation sEV sizes suggesting that electroporation of siRNAs into sEVs does not cause aggregation or voltage-induced damage to sEVs in our system.…”

Section: Discussionmentioning

confidence: 99%

Small extracellular vesicle-mediated ITGB6 siRNA delivery downregulates the αVβ6 integrin and inhibits adhesion and migration of recipient prostate cancer cells

Krishn

Garcia

Naranjo

et al. 2022

Cancer Biology & Therapy

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The αVβ6 integrin, an epithelial-specific cell surface receptor absent in normal prostate and expressed during prostate cancer (PrCa) progression, is a therapeutic target in many cancers. Here, we report that transcript levels of ITGB6 (encoding the β6 integrin subunit) are significantly increased in metastatic castrate-resistant androgen receptor-negative prostate tumors compared to androgen receptor-positive prostate tumors. In addition, the αVβ6 integrin protein levels are significantly elevated in androgen receptor-negative PrCa patient derived xenografts (PDXs) compared to androgen receptor-positive PDXs. In vitro , the androgen receptor-negative PrCa cells express high levels of the αVβ6 integrin compared to androgen receptor-positive PrCa cells. Additionally, expression of androgen receptor (wild type or variant 7) in androgen receptor-negative PrCa cells downregulates the expression of the β6 but not αV subunit compared to control cells. We demonstrate an efficient strategy to therapeutically target the αVβ6 integrin during PrCa progression by using short interfering RNA (siRNA) loaded into PrCa cell-derived small extracellular vesicles (sEVs). We first demonstrate that fluorescently-labeled siRNAs can be efficiently loaded into PrCa cell-derived sEVs by electroporation. By confocal microscopy, we show efficient internalization of these siRNA-loaded sEVs into PrCa cells. We show that sEV-mediated delivery of ITGB6 -targeting siRNAs into PC3 cells specifically downregulates expression of the β6 subunit. Furthermore, treatment with sEVs encapsulating ITGB6 siRNA significantly reduces cell adhesion and migration of PrCa cells on an αVβ6-specific substrate, LAP-TGFβ1. Our results demonstrate an approach for specific targeting of the αVβ6 integrin in PrCa cells using sEVs encapsulating ITGB6 -specific siRNAs.

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“…In addition to protecting payloads from enzymatic destruction, exosomes also enable them to target cells in a passive and particular manner. Overall, this is achieved due to their distinctive double-layered membrane structure ( Liang et al, 2020 ; Han et al, 2021 ).…”

Section: The Therapeutic Promise Of Exosomes Generated From Mscs In a Variety Of Tissuesmentioning

confidence: 99%

Mesenchymal Stem Cell-Derived Exosomes as a Novel Strategy for the Treatment of Intervertebral Disc Degeneration

Gao

et al. 2022

Front. Cell Dev. Biol.

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Intervertebral disc degeneration (IVDD) has been reported to be the most prevalent contributor to low back pain, posing a significant strain on the healthcare systems on a global scale. Currently, there are no approved therapies available for the prevention of the progressive degeneration of intervertebral disc (IVD); however, emerging regenerative strategies that aim to restore the normal structure of the disc have been fundamentally promising. In the last decade, mesenchymal stem cells (MSCs) have received a significant deal of interest for the treatment of IVDD due to their differentiation potential, immunoregulatory capabilities, and capability to be cultured and regulated in a favorable environment. Recent investigations show that the pleiotropic impacts of MSCs are regulated by the production of soluble paracrine factors. Exosomes play an important role in regulating such effects. In this review, we have summarized the current treatments for disc degenerative diseases and their limitations and highlighted the therapeutic role and its underlying mechanism of MSC-derived exosomes in IVDD, as well as the possible future developments for exosomes.

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Targeted inhibition of SIRT6 via engineered exosomes impairs tumorigenesis and metastasis in prostate cancer

Cited by 66 publications

References 53 publications

The Role of Extracellular Vesicles in the Pathogenesis, Diagnosis, and Treatment of Osteoarthritis

The Role of Extracellular Vesicles in the Pathogenesis, Diagnosis, and Treatment of Osteoarthritis

Small extracellular vesicle-mediated ITGB6 siRNA delivery downregulates the αVβ6 integrin and inhibits adhesion and migration of recipient prostate cancer cells

Mesenchymal Stem Cell-Derived Exosomes as a Novel Strategy for the Treatment of Intervertebral Disc Degeneration

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