Cell-free synthesis of connexin 43-integrated exosome-mimetic nanoparticles for siRNA delivery

Lu, Mengmeng; Xi, Zhao; Xing, Haonan; Liu, Hui; Lang, Lang; Yang, Tianzhi; Xun, Zhe; Wang, Dongkai; Ding, Pingtian

doi:10.1016/j.actbio.2019.07.006

Cited by 44 publications

(37 citation statements)

References 70 publications

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“…In addition to mimic the functions of exosomes to activate molecular pathways, liposome-based artificial exosomes can also be used for drug or gene delivery. To develop EM NPs for siRNA delivery, Lu et al constructed liposomes coated chitosan NPs as exosome-mimicking membranes to protect siRNA cargo and introduced to synthesized plasmids encoding connexin 43 (Cx43), a transmembrane protein, to direct the transcription, translation, and integration of Cx43 in the lipid layers in EM [ 86 ]. Integrated Cx43 worked functionally in cellular transport and facilitated the delivery of siRNA in EM to Cx43-expressing U87 MG cells.…”

Section: Artificial Exosomes By Nanobiotechnologymentioning

confidence: 99%

Artificial exosomes for translational nanomedicine

Liu

et al. 2021

J Nanobiotechnol

145

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Exosomes are lipid bilayer membrane vesicles and are emerging as competent nanocarriers for drug delivery. The clinical translation of exosomes faces many challenges such as massive production, standard isolation, drug loading, stability and quality control. In recent years, artificial exosomes are emerging based on nanobiotechnology to overcome the limitations of natural exosomes. Major types of artificial exosomes include ‘nanovesicles (NVs)’, ‘exosome-mimetic (EM)’ and ‘hybrid exosomes (HEs)’, which are obtained by top-down, bottom-up and biohybrid strategies, respectively. Artificial exosomes are powerful alternatives to natural exosomes for drug delivery. Here, we outline recent advances in artificial exosomes through nanobiotechnology and discuss their strengths, limitations and future perspectives. The development of artificial exosomes holds great values for translational nanomedicine.

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Section: Artificial Exosomes By Nanobiotechnologymentioning

confidence: 99%

Artificial exosomes for translational nanomedicine

Liu

et al. 2021

J Nanobiotechnol

145

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“…Calcium phosphate (Zhang et al, 2017) and liposomes (Lu et al, 2019) were conventionally used as transfection reagents for cells. Recently, they were reported to efficiently load DNA into exosomes.…”

Section: Transfection Reagent-based Encapsulationmentioning

confidence: 99%

Exosomes, a New Star for Targeted Delivery

Chen

Wang

Zeng

et al. 2021

Front. Cell Dev. Biol.

122

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Exosomes are cell-secreted nanoparticles (generally with a size of 30–150 nm) bearing numerous biological molecules including nucleic acids, proteins and lipids, which are thought to play important roles in intercellular communication. As carriers, exosomes hold promise as advanced platforms for targeted drug/gene delivery, owing to their unique properties, such as innate stability, low immunogenicity and excellent tissue/cell penetration capacity. However, their practical applications can be limited due to insufficient targeting ability or low efficacy in some cases. In order to overcome these existing challenges, various approaches have been applied to engineer cell-derived exosomes for a higher selectivity and effectiveness. This review presents the state-of-the-art designs and applications of advanced exosome-based systems for targeted cargo delivery. By discussing experts’ opinions, we hope this review will inspire the researchers in this field to develop more practical exosomal delivery systems for clinical applications.

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“…107 Integration of exosomes with connexin 43 (Cx43), a membrane protein that assembles to form hexametric channels, allows exosomes to dock at the gap junction pore embedded in the plasma membrane of recipient cells, and therefore provides another route for direct cytoplasmic transfer of exosome payload. 108 As for internalized exosomes following the endosomal traffic route, the ability of the cargo to escape before lysosomal degradation is another challenge. Exosomes complexed with cationic lipids together with a pH-sensitive fusogenic peptide, GALA, increased exosome-endosome fusion and, therefore, aided in the cytosolic release of cargo.…”

Section: Enhanced Intracellular Deliverymentioning

confidence: 99%

“…107 (D) Exosomes expressing connexin-43 that forms hexametric channels to allow exosome to dock to gap junction pore on plasma membrane and, therefore, enable direct cytoplasmic transfer of cargo. 108 In addition, (E) integrating fusogenic peptide (eg, GALA peptide) facilitates exosome escape of payload before lysosomal degradation. 109 submit your manuscript | www.dovepress.com…”

Section: Enhanced Intracellular Deliverymentioning

confidence: 99%

<p>Advances in Exosome-Based Drug Delivery and Tumor Targeting: From Tissue Distribution to Intracellular Fate</p>

Shao

Zaro

Shen

2020

IJN

149

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Exosomes or small extracellular vesicles are considered a new generation of bioinspired-nanoscale drug delivery system (DDS). Endogenous exosomes function as signalosomes since they convey signals via ligands or adhesion molecules located on the exosomal membrane, or packaged inside the exosome. Recently, exosome membrane modification, therapeutic payloads encapsulation, and modulation of in vivo disposition of exosomes have been extensively investigated, among which significant advances have been made to optimize exosome-mediated delivery to solid tumors. Exosomes, specifically tumor cell-derived exosomes, are presumed to have tumor-preferential delivery due to the homotypic features. However, quality attributes that dictate the tissue distribution, cell typeselective uptake, and intracellular payload release of the administered exosomes, as well as the spatiotemporal information regarding exosome fate in vivo, remain to be further investigated. This review summarizes recent advances in developing exosomes as drug delivery platforms with a focus on tumor targeting. The pharmacokinetic features of naive exosomes and factors influencing their intracellular fate are summarized. Recent strategies to improve tumor targeting of exosomes are also reviewed in the context of the biological features of tumor and tumor microenvironment (TME). Selected approaches to augment tumor tissue deposition of exosomes, as well as methods to enhance intracellular payload delivery, are summarized with emphasis on the underlying mechanisms (eg, passive or active targeting, endosomal escape, etc.). In conclusion, this review highlights recently reported tumortargeting strategies of exosome-based drug delivery, and it's in the hope that multiple approaches might be employed in a synergistic combination in the development of exosomebased cancer therapy.

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Cell-free synthesis of connexin 43-integrated exosome-mimetic nanoparticles for siRNA delivery

Cited by 44 publications

References 70 publications

Artificial exosomes for translational nanomedicine

Artificial exosomes for translational nanomedicine

Exosomes, a New Star for Targeted Delivery

<p>Advances in Exosome-Based Drug Delivery and Tumor Targeting: From Tissue Distribution to Intracellular Fate</p>

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