Exosome engineering: Current progress in cargo loading and targeted delivery

Fu, Shengyang; Wang, Yi; Xia, Xiaohuan; Zheng, Jialin

doi:10.1016/j.impact.2020.100261

Cited by 247 publications

(257 citation statements)

References 197 publications

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“…In addition, exosomes can overcome both hematoencephalic [ 29 ] and placental barriers [ 30 , 31 ]. Exosome surface can also be engineered for targeted delivery and thus, tissue-specific biodistribution [ 32 ].…”

Section: Introductionmentioning

confidence: 99%

Bovine Milk-Derived Exosomes as a Drug Delivery Vehicle for miRNA-Based Therapy

Pozo-Acebo

Hazas

Tomé‐Carneiro

et al. 2021

IJMS

100

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MicroRNAs (miRNAs) are small non-coding RNAs with a known role as mediators of gene expression in crucial biological processes, which converts them into high potential contenders in the ongoing search for effective therapeutic strategies. However, extracellular RNAs are unstable and rapidly degraded, reducing the possibility of successfully exerting a biological function in distant target cells. Strategies aimed at enhancing the therapeutic potential of miRNAs include the development of efficient, tissue-specific and nonimmunogenic delivery methods. Since miRNAs were discovered to be naturally transported within exosomes, a type of extracellular vesicle that confers protection against RNase degradation and increases miRNA stability have been proposed as ideal delivery vehicles for miRNA-based therapy. Although research in this field has grown rapidly in the last few years, a standard, reproducible and cost-effective protocol for exosome isolation and extracellular RNA delivery is lacking. We aimed to evaluate the use of milk-derived extracellular vesicles as vehicles for extracellular RNA drug delivery. With this purpose, exosomes were isolated from raw bovine milk, combining ultracentrifugation and size exclusion chromatography (SEC) methodology. Isolated exosomes were then loaded with exogenous hsa-miR148a-3p, a highly expressed miRNA in milk exosomes. The suitability of exosomes as delivery vehicles for extracellular RNAs was tested by evaluating the absorption of miR-148a-3p in hepatic (HepG2) and intestinal (Caco-2) cell lines. The potential exertion of a biological effect by miR-148a-3p was assessed by gene expression analysis, using microarrays. Results support that bovine milk is a cost-effective source of exosomes which can be used as nanocarriers of functional miRNAs with a potential use in RNA-based therapy. In addition, we show here that a combination of ultracentrifugation and SEC technics improve exosome enrichment, purity, and integrity for subsequent use.

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Section: Introductionmentioning

confidence: 99%

Bovine Milk-Derived Exosomes as a Drug Delivery Vehicle for miRNA-Based Therapy

Pozo-Acebo

Hazas

Tomé‐Carneiro

et al. 2021

IJMS

100

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“…Exogenous drug loading techniques vary depending on the target molecules of interest such as proteins, small molecules, and nucleic acids-specifically miRNA. Some of the mechanical methods used to load desired cargos into EVs include incubation at room temperature, electroporation, sonication, transfection, saponin permeabilization, and mechanical extrusion [ 78 , 81 , 82 , 83 , 84 ]. Electroporation, the guidance of proteins and signature sequences, producing hybrid EVs with lysosomes, transfecting donor cells, and transfection with commercialized reagents, are methods to load nucleic acids into EVs [ 81 ].…”

Section: Extracellular Vesicle-based Drug Delivery Systemsmentioning

confidence: 99%

“…Electroporation, the guidance of proteins and signature sequences, producing hybrid EVs with lysosomes, transfecting donor cells, and transfection with commercialized reagents, are methods to load nucleic acids into EVs [ 81 ]. Drug-loading strategies include incubation, ultrasonic treatment, eddy current oscillation, and direct mixing [ 78 , 83 , 84 ]. Ultrasonic treatment was discovered to have increased the drug paclitaxel’s load capacity and supported the release of EVs excreted by macrophages [ 81 ].…”

Section: Extracellular Vesicle-based Drug Delivery Systemsmentioning

confidence: 99%

Challenges in Biomaterial-Based Drug Delivery Approach for the Treatment of Neurodegenerative Diseases: Opportunities for Extracellular Vesicles

Kumar

Zhou

Zhi

et al. 2020

IJMS

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Biomaterials have been the subject of numerous studies to pursue potential therapeutic interventions for a wide variety of disorders and diseases. The physical and chemical properties of various materials have been explored to develop natural, synthetic, or semi-synthetic materials with distinct advantages for use as drug delivery systems for the central nervous system (CNS) and non-CNS diseases. In this review, an overview of popular biomaterials as drug delivery systems for neurogenerative diseases is provided, balancing the potential and challenges associated with the CNS drug delivery. As an effective drug delivery system, desired properties of biomaterials are discussed, addressing the persistent challenges such as targeted drug delivery, stimuli responsiveness, and controlled drug release in vivo. Finally, we discuss the prospects and limitations of incorporating extracellular vesicles (EVs) as a drug delivery system and their use for biocompatible, stable, and targeted delivery with limited immunogenicity, as well as their ability to be delivered via a non-invasive approach for the treatment of neurodegenerative diseases.

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“…The ability of EVs to cross the BBB has contributed to exploring the therapeutic potential of EVs in brain diseases more intensely [ 108 ]. Furthermore, the perception that EVs can be engineered and produced with a specific molecular cargo has propelled research into therapeutic applications of EVs [ 109 , 110 ]. The therapeutic potential of EVs in the field of neurodegenerative diseases has been recently reviewed [ 111 ].…”

Section: Evs In Therapymentioning

confidence: 99%

“…Interestingly, the distinctive feature of EVs, particularly exosomes, of crossing the BBB provides a tremendous advantage in designing EV based diagnostics and therapeutics for CNS disorders. Recent developments in the field of exosome engineering [ 110 ] will further catalyze the development of EV-based therapeutics. These technologies make it possible to generate exosomes customized for a specific CNS pathology.…”

Section: Conclusion/final Remarksmentioning

confidence: 99%

Extracellular Vesicles in CNS Developmental Disorders

Gomes

Sangani

Fernandes

et al. 2020

IJMS

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The central nervous system (CNS) is the most complex structure in the body, consisting of multiple cell types with distinct morphology and function. Development of the neuronal circuit and its function rely on a continuous crosstalk between neurons and non-neural cells. It has been widely accepted that extracellular vesicles (EVs), mainly exosomes, are effective entities responsible for intercellular CNS communication. They contain membrane and cytoplasmic proteins, lipids, non-coding RNAs, microRNAs and mRNAs. Their cargo modulates gene and protein expression in recipient cells. Several lines of evidence indicate that EVs play a role in modifying signal transduction with subsequent physiological changes in neurogenesis, gliogenesis, synaptogenesis and network circuit formation and activity, as well as synaptic pruning and myelination. Several studies demonstrate that neural and non-neural EVs play an important role in physiological and pathological neurodevelopment. The present review discusses the role of EVs in various neurodevelopmental disorders and the prospects of using EVs as disease biomarkers and therapeutics.

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Exosome engineering: Current progress in cargo loading and targeted delivery

Cited by 247 publications

References 197 publications

Bovine Milk-Derived Exosomes as a Drug Delivery Vehicle for miRNA-Based Therapy

Bovine Milk-Derived Exosomes as a Drug Delivery Vehicle for miRNA-Based Therapy

Challenges in Biomaterial-Based Drug Delivery Approach for the Treatment of Neurodegenerative Diseases: Opportunities for Extracellular Vesicles

Extracellular Vesicles in CNS Developmental Disorders

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