Systemic delivery of microRNA-21 antisense oligonucleotides to the brain using T7-peptide decorated exosomes

Kim, Gyeungyun; Kim, Minkyung; Lee, Mi Kyung; Byun, Jung Woo; Hwang, Do Won; Lee, Minhyung

doi:10.1016/j.jconrel.2019.11.009

Cited by 194 publications

(156 citation statements)

References 31 publications

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“…T7exosomes had a higher delivery efficiency to glioblastoma cells in comparison to the unmodified exosomes or RVG-decorated exosomes in vitro. Similar observations were obtained in vivo, where the delivery of AMO-21 by exosomes via an intravenous injection led to a reduction in the miR-21 levels, followed by the reduction of tumor size (Kim et al, 2020). Finally, muscle-specific peptide (MSP) identified by in vivo phage display (ASSLNIA) can also be fused with Lamp2b for muscle-specific delivery of exosomes (Alvarez-Erviti et al, 2011b).…”

Section: Brain-homing Signals For Exosomessupporting

confidence: 65%

“…Although exosomes were evaluated in terms of the therapeutic function in such CNS conditions as glioblastoma (Kim et al, 2020), these and other natural nanovesicles have not been extensively characterized as delivery vehicles of therapeutic agents for LSD. A single study focused on exosome-based delivery of a lysosomal enzyme for LSD treatment, in which lysosomal β-glucocerebrosidase (GBA) was fused to a protein that anchored it to the exosomes, termed vesicular stomatitis virus glycoprotein (VSVG), without altering the protein function, but significantly increasing the levels of β-glucocerebrosidase.…”

Section: Exploring Therapeutic Evs To Treat Disorders Affecting Cnsmentioning

confidence: 99%

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CNS-Targeting Therapies for Lysosomal Storage Diseases: Current Advances and Challenges

Edelmann

Maegawa

2020

Front. Mol. Biosci.

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During the past decades, several therapeutic approaches have been developed and made rapidly available for many patients afflicted with lysosomal storage disorders (LSDs), inborn organelle disorders with broad clinical manifestations secondary to the progressive accumulation of undegraded macromolecules within lysosomes. These conditions are individually rare, but, collectively, their incidence ranges from 1 in 2,315 to 7,700 live-births. Most LSDs are manifested by neurological symptoms or signs, including developmental delay, seizures, acroparesthesia, motor weakness, and extrapyramidal signs. The chronic and later-onset clinical forms are at one end of the continuum spectrum and are characterized by a subtle and slow progression of neurological symptoms. Due to its inherent physiological properties, unfortunately, the blood-brain barrier (BBB) constitutes a significant obstacle for current and upcoming therapies to achieve the central nervous system (CNS) and treat neurological problems so prevalent in these conditions. To circumvent this limitation, several strategies have been developed to make the therapeutic agent achieve the CNS. This narrative will provide an overview of current therapeutic strategies under development to permeate the BBB, and address and unmet need for treatment of the progressive neurological manifestations, which are so prevalent in these inherited lysosomal disorders.

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Section: Brain-homing Signals For Exosomessupporting

confidence: 65%

Section: Exploring Therapeutic Evs To Treat Disorders Affecting Cnsmentioning

confidence: 99%

CNS-Targeting Therapies for Lysosomal Storage Diseases: Current Advances and Challenges

Edelmann

Maegawa

2020

Front. Mol. Biosci.

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“…of T7-decorated exosomes compared with unmodifiedexosomes in the treatment of glioblastoma. 36 These findings indicate that T7-modified nanoparticles could enhance the uptake efficiency of esophageal cancer cells.…”

mentioning

confidence: 79%

<p>Novel T7-Modified pH-Responsive Targeted Nanosystem for Co-Delivery of Docetaxel and Curcumin in the Treatment of Esophageal Cancer</p>

Deng¹,

Zhu²,

Yu³

et al. 2020

IJN

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Background: Although single-drug chemotherapy is still an effective treatment for esophageal cancer, its long-term application is limited by severe side-effects, poor bioavailability, and drug-resistance. Increasing attention has been paid to nanomedicines because of their good biological safety, targeting capabilities, and high-efficiency loading of multiple drugs. Herein, we have developed a novel T7 peptide-modified pH-responsive targeting nanosystem co-loaded with docetaxel and curcumin for the treatment of esophageal cancer. Methods: Firstly, CM-β-CD-PEI-PEG-T7/DTX/CUR (T7-NP-DC) was synthesized by the double emulsion (W/O/W) method. The targeting capacity of the nanocarrier was then investigated by in vitro and in vivo assays using targeted (T7-NP) and non-targeted nanoparticles (NP). Furthermore, the anti-tumor efficacy of T7-NP-DC was studied using esophageal cancer cells (KYSE150 and KYSE510) and a KYSE150 xenograft tumor model. Results: T7-NP-DC was synthesized successfully and its diameter was determined to be about 100 nm by transmission electron microscopy and dynamic light scattering. T7-NP-DC with docetaxel and curcumin loading of 10% and 6.1%, respectively, had good colloidal stability and exhibited pH-responsive drug release. Good biosafety was observed, even when the concentration was as high as 800 μg/mL. Significant enhancement of T7-NP uptake was observed 6 hours after intravenous injection compared with NP. In addition, the therapeutic efficacy of T7-NP-DC was better than NP-DC and docetaxel in terms of growth suppression in the KYSE150 esophageal cancer model. Conclusion: The findings demonstrated that T7-NP-DC is a promising, non-toxic, and controllable nanoparticle that is capable of simultaneous delivery of the chemotherapy drug, docetaxel, and the Chinese Medicine, curcumin, for treatment of esophageal cancer. This novel T7-modified targeting nanosystem releases loaded drugs when exposed to the acidic microenvironment of the tumor and exerts a synergistic anti-tumor effect. The data indicate that the nanomaterials can safely exert synergistic anti-tumor effects and provide an excellent therapeutic platform for combination therapy of esophageal cancer.

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“…Hereby, intravenous administration of EVs from MSCs has been repeatedly successful towards the delivery of EVs, for instance, carrying different miRNAs, to the CNS [ 59 , 102 , 103 , 104 ]. Similarly, other studies described the intravenous delivery to the CNS of EVs isolated from adipose tissue stem cells [ 105 ], HEK293T cells [ 106 ], urinary stem cells [ 40 ], dendritic cells [ 107 ] and rat serum [ 108 ]. However, it is worth mentioning that most of these did not evaluate whether the same experimental approach may result in effects in other tissues.…”

Section: Administration and Biodistributionmentioning

confidence: 99%

Recent Advances in Extracellular Vesicles as Drug Delivery Systems and Their Potential in Precision Medicine

et al. 2020

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Extracellular vesicles (EVs) are membrane-bilayered nanoparticles released by most cell types. Recently, an enormous number of studies have been published on the potential of EVs as carriers of therapeutic agents. In contrast to systems such as liposomes, EVs exhibit less immunogenicity and higher engineering potential. Here, we review the most relevant publications addressing the potential and use of EVs as a drug delivery system (DDS). The information is divided based on the key steps for designing an EV-mediated delivery strategy. We discuss possible sources and isolation methods of EVs. We address the administration routes that have been tested in vivo and the tissue distribution observed. We describe the current knowledge on EV clearance, a significant challenge towards enhancing bioavailability. Also, EV-engineering approaches are described as alternatives to improve tissue and cell-specificity. Finally, a summary of the ongoing clinical trials is performed. Although the application of EVs in the clinical practice is still at an early stage, a high number of studies in animals support their potential as DDS. Thus, better treatment options could be designed to precisely increase target specificity and therapeutic efficacy while reducing off-target effects and toxicity according to the individual requirements of each patient.

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Systemic delivery of microRNA-21 antisense oligonucleotides to the brain using T7-peptide decorated exosomes

Cited by 194 publications

References 31 publications

CNS-Targeting Therapies for Lysosomal Storage Diseases: Current Advances and Challenges

CNS-Targeting Therapies for Lysosomal Storage Diseases: Current Advances and Challenges

<p>Novel T7-Modified pH-Responsive Targeted Nanosystem for Co-Delivery of Docetaxel and Curcumin in the Treatment of Esophageal Cancer</p>

Recent Advances in Extracellular Vesicles as Drug Delivery Systems and Their Potential in Precision Medicine

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