Research progress in membrane fusion-based hybrid exosomes for drug delivery systems

Liu, Anqi; Yang, Gang; Liu, Yuehua; Liu, Tingjiao

doi:10.3389/fbioe.2022.939441

Cited by 22 publications

(21 citation statements)

References 83 publications

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“…The western blotting and Coomassie brilliant blue staining results con rmed a similar protein expression on HE and exosome. However, it is reported that the shear stress generated during the extrusion process may damage the protein integrity of exosomes [37]. Here, the intensity of the protein bands of HE and exosome in both western blotting assay and Coomassie brilliant blue staining was comparable, indicating that the membrane extrusion frequency (15 times) has little impact on protein degradation.…”

Section: Discussionmentioning

confidence: 66%

Paclitaxel-loaded hybrid exosome for targeted chemotherapy of triple-negative breast cancer

Liu

Tang

et al. 2022

Preprint

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Background: Triple-negative breast cancer (TNBC) is a highly invasive malignant tumor with bleak prognosis.Paclitaxel (PTX) is the first-line chemotherapeutic drug for TNBC management. It is of great significance to develop carriers for targeted delivery of PTX to enhance the anti-tumor efficacy and reduce the side effects for TNBC management. Exosomes are small extracellular vesicles and emerging competent nanocarriers for targeted drug delivery. However, the application of exosomes has been challenged by the production, drug loading and quality control. The introduction of synthetic nanomaterials may help to overcome the limitations of exosomes and generate alternatives. Herein, we performed a biohybrid approach to fuse exosomeswith liposomes to produce hybrid exosome (HE) with improved PTX loading capacity and enhanced tumor-targeting ability for TNBC chemotherapy. Methods:HE and PTX-loaded HE (PTX-HE) were prepared by co-extrusion of exosomes with liposome (lipo) or PTX-loaded liposome (PTX-lipo) respectively. The size distribution of HE was measured by nanoparticle tracking analysis (NTA) and dynamic laser-light scattering (DLS). The morphology was observed by transmission electron microscopy (TEM). The protein profile of HE was determined by western blot and Coomassie Blue staining. Drug loading capacity and encapsulation efficiency were measured by high-performance liquid chromatography (HPLC). Cellular uptake, tumor cell killing effect and anti-migration ability of PTX-HE were evaluated in vitro. Biodistribution, anti-tumor therapeutic efficacy and safety of PTX-HE were evaluated in orthotopic TNBC mice models. Results:The characterization results manifested HE was spherical structure with uniform size distribution (157.28 nm). HE had improved loading capacity (6.20 ± 0.79%) and higher encapsulation efficiency (86.79 ± 11.07%) of PTX than lipo. More importantly, PTX-HE possessed higher cellular uptake efficiency, lower IC50 (4.32 ± 0.48 μg/mL) and stronger anti-migration ability (cell mobility: 16%) as compared with PTX-lipo. In TNBC-bearing mice, PTX-HE accumulated at tumor sites and suppressed tumor growth (tumor inhibition rate: 60%) with minimal systemic toxicity. Conclusions: HE exhibits improved drug loading capacity, targeting ability and cancer cell-killing effect. Overall, HE developed by fusing exosomes with liposomes provides a promising strategy for the large-scale generation of exosome alternatives as drug carriers for targeted chemotherapy.

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Section: Discussionmentioning

confidence: 66%

Paclitaxel-loaded hybrid exosome for targeted chemotherapy of triple-negative breast cancer

Liu

Tang

et al. 2022

Preprint

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“…The natural incubation process for membrane fusion involves the spontaneous fusion of lipid membranes through electrostatic or hydrophobic interactions based on the physicochemical components of mixed vesicles. This process has a low risk of damaging the vesicles and their contents but has a low fusion efficiency [ 49 ]. Lin et al used this process to create an exosome–liposome hybrid for gene therapy, encapsulating the CRISPR/Cas9 expression vector [ 71 ].…”

Section: Strategies Of Membrane Fusionmentioning

confidence: 99%

“…The fusion of EVs with liposomes, exosomes, and cell membranes offers an increased loading capacity, stability, and biocompatibility, with reduced immunogenicity [ 45 , 46 , 47 ]. While there were previous reviews that briefly mentioned the potential of liposome and exosome fusion as a novel approach for therapeutic applications [ 48 , 49 , 50 ], no previous review has focused on the EVs fusion strategy and its biomedical applications in diagnostics and therapeutics. This study focuses on bioengineering EVs through membrane fusion strategies.…”

Section: Introductionmentioning

confidence: 99%

Tuning the Extracellular Vesicles Membrane through Fusion for Biomedical Applications

Karmacharya

Kumar

Cho

2023

JFB

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Membrane fusion is one of the key phenomena in the living cell for maintaining the basic function of life. Extracellular vesicles (EVs) have the ability to transfer information between cells through plasma membrane fusion, making them a promising tool in diagnostics and therapeutics. This study explores the potential applications of natural membrane vesicles, EVs, and their fusion with liposomes, EVs, and cells and introduces methodologies for enhancing the fusion process. EVs have a high loading capacity, bio-compatibility, and stability, making them ideal for producing effective drugs and diagnostics. The unique properties of fused EVs and the crucial design and development procedures that are necessary to realize their potential as drug carriers and diagnostic tools are also examined. The promise of EVs in various stages of disease management highlights their potential role in future healthcare.

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“…Besides larger size, hybrid exosomes often possess slightly reduced ZP compared to liposomes due to the initial negative charges of the exosomes ( Bhattacharjee, 2016 ). The following exosomal imaging will reveal confirmation of the fusion ( Bhattacharjee, 2016 ; Liu et al, 2022 ). Flow cytometry and western blot analysis will further confirm the anti-ErbB4 ligand’s existence on the surface of liposome-exosome hybrid extracts ( Lin et al, 2018 ; Alghuthaymi et al, 2021 ).…”

Section: Evaluation Of Strategymentioning

confidence: 99%

Hypoxia-sensitive miRNA regulation via CRISPR/dCas9 loaded in hybrid exosomes: A novel strategy to improve embryo implantation and prevent placental insufficiency during pregnancy

Yaghoobi

Nazerian

Meymand

et al. 2023

Front. Cell Dev. Biol.

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Assisted reproductive techniques as a new regenerative medicine approach have significantly contributed to solving infertility problems that affect approximately 15% of couples worldwide. However, the success rate of an in vitro fertilization (IVF) cycle remains only about 20%–30%, and 75% of these losses are due to implantation failure (the crucial rate-limiting step of gestation). Implantation failure and abnormal placenta formation are mainly caused by defective adhesion, invasion, and angiogenesis. Placental insufficiency endangers both the mother’s and the fetus’s health. Therefore, we suggested a novel treatment strategy to improve endometrial receptivity and implantation success rate. In this strategy, regulating mir-30d expression as an upstream transcriptomic modifier of the embryo implantation results in modified expression of the involved genes in embryonic adhesion, invasion, and angiogenesis and consequently impedes implantation failure. For this purpose, “scaffold/matrix attachment regions (S/MARs)” are employed as non-viral episomal vectors, transfecting into trophoblasts by exosome-liposome hybrid carriers. These vectors comprise CRISPR/dCas9 with a guide RNA to exclusively induce miR-30d gene expression in hypoxic stress conditions. In order to avoid concerns about the fetus’s genetic manipulation, our vector would be transfected specifically into the trophoblast layer of the blastocyst via binding to trophoblast Erb-B4 receptors without entering the inner cell mass. Additionally, S/MAR episomal vectors do not integrate with the original cell DNA. As an on/off regulatory switch, a hypoxia-sensitive promoter (HRE) is localized upstream of dCas9. The miR-30d expression increases before and during the implantation and placental insufficiency conditions and is extinguished after hypoxia elimination. This hypothesis emphasizes that improving the adhesion, invasion, and angiogenesis in the uterine microenvironment during pregnancy will result in increased implantation success and reduced placental insufficiency, as a new insight in translational medicine.

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Research progress in membrane fusion-based hybrid exosomes for drug delivery systems

Cited by 22 publications

References 83 publications

Paclitaxel-loaded hybrid exosome for targeted chemotherapy of triple-negative breast cancer

Paclitaxel-loaded hybrid exosome for targeted chemotherapy of triple-negative breast cancer

Tuning the Extracellular Vesicles Membrane through Fusion for Biomedical Applications

Hypoxia-sensitive miRNA regulation via CRISPR/dCas9 loaded in hybrid exosomes: A novel strategy to improve embryo implantation and prevent placental insufficiency during pregnancy

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