Functional siRNA Delivery by Extracellular Vesicle–Liposome Hybrid Nanoparticles

Advanced Healthcare Materials, Год журнала: 2021, Номер 11(5)

Опубликована: Авг. 11, 2021

The therapeutic use of RNA interference is limited by the inability siRNA molecules to reach their site action, cytosol target cells. Lipid nanoparticles, including liposomes, are commonly employed as carrier systems overcome this hurdle, although widespread remains due a lack delivery efficiency. More recently, nature's own carriers RNA, extracellular vesicles (EVs), increasingly being considered alternative vehicles intrinsic properties. However, they difficult load with exogenous cargo. Here, EV-liposome hybrid nanoparticles (hybrids) prepared and evaluated an system combining properties both liposomes EVs. It shown that hybrids spherical particles encapsulating siRNA, contain EV-surface makers, functionally deliver different cell types. functional behavior hybrids, in terms cellular uptake, toxicity, gene-silencing efficacy, altered compared varies among recipient Moreover, produced cardiac progenitor (CPC) derived-EVs retain attributed CPC-EVs such activation endothelial signaling migration. To conclude, combine benefits synthetic biological drug might serve future siRNA.

Язык: Английский

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Exosomes as bio-inspired nanocarriers for RNA delivery: preparation and applications

Journal of Translational Medicine, Год журнала: 2022, Номер 20(1)

Опубликована: Март 14, 2022

Abstract Nanocarriers as drug/biomolecule delivery systems have been significantly developed during recent decades. Given the stability, reasonable efficiency, and safety of nanocarriers, there are several barriers in fulfillment successful clinical application these systems. These challenges encouraged drug researchers to establish innovative nanocarriers with longer circulation time, high compatibility. Exosomes extracellular nanometer-sized vesicles released through various cells. serve possessing great potential overcome some obstacles encountered gene due their natural affinity recipient cells inherent capability shuttle genes, lipids, proteins, RNAs between So far, has a lot valuable research on by exosomes, but RNA delivery, especially mRNA, is very limited. Since mRNA-based vaccines therapies recently gained particular prominence diseases, it essential find suitable system large size destructive nature nucleic acids. That's why we're going take look at unique features exosomes isolation loading methods, embrace this idea that exosome-mediated would be introduced efficient strategy disease treatment within near future. Graphical

Язык: Английский

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Cell-derived nanovesicle-mediated drug delivery to the brain: Principles and strategies for vesicle engineering

Molecular Therapy, Год журнала: 2022, Номер 31(5), С. 1207 - 1224

Опубликована: Окт. 17, 2022

Developing strategies toward safe and effective drug delivery into the central nervous system (CNS) with improved targeting abilities reduced off-target effects is crucial. CNS-targeted carriers made of synthetic molecules raise concerns about their biodegradation, clearance, immune responses, neurotoxicity. Cell-derived nanovesicles (CDNs) have recently been applied in delivery, because intrinsic stability, biocompatibility, inherent homing capability, ability to penetrate through biological barriers, including blood-brain barrier. Among these CDNs, extracellular vesicles exosomes are most studied surface can be engineered modified cater brain targeting. In this review, we focus on application CDNs brain-targeted treat neurological diseases. We cover developed methods exosome derivation engineering, exosome-like particles, hybrid exosomes, exosome-associated adeno-associated viruses, envelope protein nanocages. Finally, discuss limitations project future development CDN-based systems, conclude that hold great potential treatment

Язык: Английский

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Cancer Nanomedicine: Emerging Strategies and Therapeutic Potentials

Molecules, Год журнала: 2023, Номер 28(13), С. 5145 - 5145

Опубликована: Июнь 30, 2023

Cancer continues to pose a severe threat global health, making pursuing effective treatments more critical than ever. Traditional therapies, although pivotal in managing cancer, encounter considerable challenges, including drug resistance, poor solubility, and difficulties targeting tumors, specifically limiting their overall efficacy. Nanomedicine's application cancer therapy signals new epoch, distinguished by the improvement of specificity, efficacy, tolerability treatments. This review explores mechanisms advantages nanoparticle-mediated delivery, highlighting passive active strategies. Furthermore, it transformative potential nanomedicine tumor therapeutics, delving into its applications across various treatment modalities, surgery, chemotherapy, immunotherapy, radiotherapy, photodynamic photothermal therapy, gene as well diagnosis imaging. Meanwhile, outlook therapeutics is discussed, emphasizing need for addressing toxicity concerns, improving delivery strategies, enhancing carrier stability controlled release, simplifying nano-design, exploring novel manufacturing technologies. Overall, integrating holds immense revolutionizing patient outcomes.

Язык: Английский

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Cancer signaling, cell/gene therapy, diagnosis and role of nanobiomaterials

Advances in Biology & Earth Sciences, Год журнала: 2024, Номер 9(Special Issue), С. 11 - 34

Опубликована: Апрель 11, 2024

An important characteristic of cancer is aberrant metabolism. Drug resistance, stem cells, metastasis and tumorigenesis are all significantly impacted by abnormal metabolism, which includes enhanced anabolic pathways aerobic glycolysis. The Hippo pathway, Myc PI3K/AKT recognized oncogenic signaling networks that control the expression metabolic genes increase level activity enzymes. On other hand, result in disruptions to internal signal transduction providing energy, building blocks redox capabilities necessary for uncontrolled cell proliferation. Studies clinical trials being carried out investigate impact minute substances or dietary modifications, such as calorie restriction, fasting intermittent fasting, on inhibition phenotypes malignancies remarkably diverse, much like genetic variability. Genetic abnormalities a variety signals found tumor microenvironment contribute this Therefore, one main objectives contemporary therapies overcome plasticity. This overview explains relationships between biochemical emphasizes recent research properties cancer. We also present fresh justifications upcoming class medications target an our latest studies progress nanomedicine disease detection at tiny nano-bio interactions biological systems nanoparticles. Significant field has been accomplished last 20 years. However, absence thorough knowledge situation makes it difficult improve overall patient survival with nanomedicine.

Язык: Английский

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Engineering Extracellular Vesicles as Delivery Systems in Therapeutic Applications

Advanced Science, Год журнала: 2023, Номер 10(17)

Опубликована: Апрель 20, 2023

Extracellular vesicles (EVs) are transport secreted by living cells and released into the extracellular environment. Recent studies have shown that EVs serve as "messengers" in intercellular inter-organismal communication, both normal pathological processes. EVs, natural nanocarriers, can deliver bioactivators therapy with their endogenous properties. This review article describes engineering of sources, isolation method, cargo loading, boosting approach, adjustable targeting EVs. Furthermore, summarizes recent progress made EV-based delivery systems applications, including cancer, cardiovascular diseases, liver, kidney, nervous system COVID-19 emphasizes obstacles challenges therapies possible strategies.

Язык: Английский

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Sequential Targeting Hybrid Nanovesicles Composed of Chimeric Antigen Receptor T-Cell-Derived Exosomes and Liposomes for Enhanced Cancer Immunochemotherapy

ACS Nano, Год журнала: 2023, Номер 17(17), С. 16770 - 16786

Опубликована: Авг. 25, 2023

Paclitaxel (PTX)-based chemotherapy remains the main approach to treating lung cancer but systemic toxicity limits its use. As chimeric antigen receptor-T (CAR-T) cell-derived exosomes contain tumor-targeted CARs and cytotoxic granules (granzyme B perforin), they are considered potential delivery vehicles for PTX. However, low drug-loading capacity hepatotropic properties of obstacles their application extrahepatic cancer. Here, a hybrid nanovesicle named Lip-CExo@PTX was designed immunochemotherapy by fusing derived from bispecific CAR-T cells targeting both mesothelin (MSLN) programmed death ligand-1 (PD-L1) with lung-targeted liposomes. Due lung-targeting ability liposomes, over 95% intravenously administered accumulated in tissue. In addition, help anti-MSLN single-chain variable fragment (scFv), PTX inside were further delivered into MSLN-positive tumors. Notably, anti-PD-L1 scFv on blocked PD-L1 tumors avoid T cell exhaustion promoted PTX-induced immunogenic death. Furthermore, prolonged survival time tumor-bearing mice CT-26 metastatic model. Therefore, may deliver tumor through sequential targeted enhance antitumor effects, providing promising strategy

Язык: Английский

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Programming assembly of biomimetic exosomes: An emerging theranostic nanomedicine platform

Materials Today Bio, Год журнала: 2023, Номер 22, С. 100760 - 100760

Опубликована: Авг. 11, 2023

Exosomes have emerged as a promising cell-free therapeutic approach. However, challenges in large-scale production, quality control, and heterogeneity must be overcome before they can used clinically. Biomimetic exosomes containing key components of natural been assembled through extrusion, artificial synthesis, liposome fusion to address these limitations. These exosome-mimetics (EMs) possess similar morphology function but provide higher yields, faster size compared conventional exosomes. This article provides an overview the chemical biological properties various synthetic exosome systems, including nanovesicles (NVs), EMs, hybrid We highlight recent advances production applications nanobiotechnology discuss advantages, limitations, potential clinical programming assembly mimetics.

Язык: Английский

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Ongoing Clinical Trials of Nonviral siRNA Therapeutics

Bioconjugate Chemistry, Год журнала: 2023, Номер 34(7), С. 1177 - 1197

Опубликована: Июль 11, 2023

Short interfering RNAs (siRNA) are a powerful class of genetic medicines whose clinical translation can be hindered by their suboptimal delivery properties in vivo. Here, we provide clinically focused overview that summarizes ongoing siRNA trials from the perspective innovations nonviral strategies. More specifically, our review begins highlighting barriers and physiochemical make it challenging to deliver We then commentary on specific strategies, including sequence modification, ligand conjugation, nanoparticle exosomal packaging, each which used control therapies living systems. Last, summary table also highlights indication use, target, National Clinical Trial (NCT) number associated with entry. In writing this review, work aims highlight key challenges strategies for effective vivo, while simultaneously summarizing information therapy humans.

Язык: Английский

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Size matters: Functional differences of small extracellular vesicle subpopulations in cardiac repair responses

Journal of Extracellular Vesicles, Год журнала: 2024, Номер 13(1)

Опубликована: Янв. 1, 2024

Abstract Cardiac progenitor cell (CPC)‐derived small extracellular vesicles (sEVs) exhibit great potential to stimulate cardiac repair. However, the multifaceted nature of sEV heterogeneity presents a challenge in understanding distinct mechanisms underlying their regenerative abilities. Here, dual‐step multimodal flowthrough and size‐exclusion chromatography method was applied isolate separate CPC‐derived subpopulations study functional differences related repair responses. Three were identified with unique protein profiles. Functional assays for repair‐related processes demonstrated that middle‐sized smallest‐sized exhibited highest pro‐angiogenic anti‐fibrotic activities. Proteasome activity uniquely seen subpopulation. The largest‐sized subpopulation showed no effect any assays. This research uncovers existence subpopulations, each characterized by composition biological function. Enhancing our will provide valuable insights into action, ultimately accelerating translation therapeutics.

Язык: Английский

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