Extracellular vesicles as carriers of mRNA: Opportunities and challenges in diagnosis and treatment DOI Creative Commons

R.D. Kirian,

Darby Steinman,

Christopher M. Jewell

et al.

Theranostics, Journal Year: 2024, Volume and Issue: 14(5), P. 2265 - 2289

Published: Jan. 1, 2024

Extracellular vesicles (EVs) are produced by all cells in the body. These biological nanoparticles facilitate cellular communication through transport of diverse cargoes, including small molecules, proteins, and nucleic acids. mRNA cargoes have gained particular interest given their role translation functional proteins. As a biomarker platform, EVs can be found nearly biofluids-blood, mucus, urine, cerebrospinal fluid, saliva-providing real-time insight into parent cell tissue function. mRNAs carried protected from degradation, resulting improved detection compared to free mRNA, recent work demonstrates promising results using these as biomarkers for cancer, neurological diseases, infectious gynecologic obstetric outcomes. Furthermore, innate cargo carrying, targeting, barrier crossing abilities EVs, structures been proposed therapeutic carriers mRNA. Recent advances demonstrate methods loading range disease indications. Here, we review studies diagnostics therapeutics. We discuss challenges associated with diagnostic applications highlight opportunities future development.

Language: Английский

Extracellular vesicle-mediated VEGF-A mRNA delivery rescues ischaemic injury with low immunogenicity DOI Creative Commons

Yi You,

Yu Tian, Rui Guo

et al.

European Heart Journal, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 20, 2025

Abstract Background and Aims Lackluster results from recently completed gene therapy clinical trials of VEGF-A delivered by viral vectors have heightened the need to develop alternative delivery strategies. This study aims demonstrate pre-clinical efficacy safety extracellular vesicles (EVs) loaded with mRNA for treatment ischaemic vascular disease. Methods After encapsulation full-length into fibroblast-derived EVs via cellular nanoporation (CNP), collected were mouse models injury. Target tissue was verified in situ analysis protein expression. Functional rescue confirmed vivo imaging histology. The single serial demonstrated using immune-based assays. Results generated high content a CNP methodology. EV administration expression exogenous RNA hybridization elevated western blot, microscopy, enzyme-linked immunosorbent assay. Mice treated human after femoral or coronary artery ligation exhibited neovascularization tissues increased arterial perfusion improvement left ventricular function, respectively. Serial VEGF-EVs injured skin showed improved wound healing repeat administration. Importantly, as compared adeno-associated lipid nanoparticle modalities, murine did not trigger innate adaptive immune responses at injection site systemically. Conclusions that offers efficient, dose-dependent formation low immunogenicity, resulting new vessel

Language: Английский

Citations

3
Extracellular vesicles as next generation immunotherapeutics DOI
David W. Greening, Rong Xu,

Anukreity Ale

et al.

Seminars in Cancer Biology, Journal Year: 2023, Volume and Issue: 90, P. 73 - 100

Published: Feb. 10, 2023

Language: Английский

Citations

39
mRNA nanodelivery systems: targeting strategies and administration routes DOI Creative Commons
Mujie Yuan, Zeyu Han, Yan Liang

et al.

Biomaterials Research, Journal Year: 2023, Volume and Issue: 27(1)

Published: Feb. 9, 2023

With the great success of coronavirus disease (COVID-19) messenger ribonucleic acid (mRNA) vaccines, mRNA therapeutics have gained significant momentum for prevention and treatment various refractory diseases. To function efficiently in vivo overcome clinical limitations, demands safe stable vectors a reasonable administration route, bypassing multiple biological barriers achieving organ-specific targeted delivery mRNA. Nanoparticle (NP)-based systems representing leading vector approaches ensure successful intracellular to target organ. In this review, chemical modifications types advanced NPs, including lipid NPs polymers are summarized. The importance passive targeting, especially endogenous active targeting nano-delivery is emphasized, different cellular endocytic mechanisms discussed. Most importantly, based on above content physiological structure characteristics organs vivo, design strategies cells classified Furthermore, influence routes highlighted. Finally, an outlook remaining challenges future development toward therapies precision medicine provided.

Language: Английский

Citations

30
Targeting materials and strategies for RNA delivery DOI Creative Commons

Lixin Lin,

Kexin Su,

Qiang Cheng

et al.

Theranostics, Journal Year: 2023, Volume and Issue: 13(13), P. 4667 - 4693

Published: Jan. 1, 2023

RNA-based therapeutics have shown great promise in various medical applications, including cancers, infectious diseases, and metabolic diseases.The recent success of mRNA vaccines for combating the COVID-19 pandemic has highlighted value RNA drugs.However, one major challenges realizing full potential drugs is to deliver into specific organs tissues a targeted manner, which crucial achieving therapeutic efficacy, reducing side effects, enhancing overall treatment efficacy.Numerous attempts been made pursue targeting, nonetheless, lack clear guideline commonality elucidation hindered clinical translation drugs.In this review, we outline mechanisms action delivery systems summarize four key factors that influence targeting drugs.These include category vector materials, chemical structures vectors, administration routes, physicochemical properties they all notably contribute organ/tissue tropism.Furthermore, provide an overview main are currently trials, highlighting their design strategies tissue tropism applications.This review will aid understand principles systems, accelerating development future different diseases.

Language: Английский

Citations

28
Biomimetic noncationic lipid nanoparticles for mRNA delivery DOI Creative Commons

Changrong Wang,

Caiyan Zhao, Weipeng Wang

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2023, Volume and Issue: 120(51)

Published: Dec. 11, 2023

Although the tremendous progress has been made for mRNA delivery based on classical cationic carriers, excess charge density of lipids was necessary to compress through electrostatic interaction, and with it comes inevitably adverse events including highly inflammatory cytotoxic effects. How develop disruptive technologies overcome nature remains a major challenge safe efficient delivery. Here, we prepared noncationic thiourea nanoparticles (NC-TNP) by strong hydrogen bonds interaction between groups NC-TNP phosphate mRNA, abandoning hidebound traditional force construct mRNA-cationic formulation. system simple, convenient, repeatable preparation technology showed negligible cytotoxicity side Furthermore, found that could escape recycling pathway inhibit egress internalized from intracellular compartment extracellular milieu which common fact in mRNA-LNP (lipid nanoparticles) Therefore, NC-TNP-encapsulated higher gene transfection efficiency vitro vivo than Unexpectedly, spleen targeting ability accumulation ratio (spleen/liver), compared LNP. Spleen-targeting exhibited high mRNA-encoded antigen expression elicited robust immune responses. Overall, our work establishes proof concept construction good safety profiles, efficiency, spleen-targeting induce permanent humoral cell-mediated immunity disease treatments.

Language: Английский

Citations

28
Small extracellular vesicles: Yields, functionalization and applications in diabetic wound management DOI Creative Commons
Xi Liu, Wei Qian, Zijie Sun

et al.

Deleted Journal, Journal Year: 2023, Volume and Issue: 1(4)

Published: Oct. 1, 2023

Abstract Diabetic wounds have imposed a significant burden on both patients and society with prolonged healing processes hindered by dysfunctional skin repair cells. Small extracellular vesicles (sEVs), as the important media for intercellular communications, show promising therapeutic potential in treating diabetic restoring cellular functions. However, low yields limited bio‐function of sEVs greatly challenge their large‐scale clinical use. Here, we briefly overview biogenesis uptake sEVs, emphasize current advances improving optimizing function engineering approaches, summarize applications engineered wound treatment. Furthermore, undissolved issues during transformation are also discussed. This critical review aims to provide meaningful guidance future management wounds.

Language: Английский

Citations

25
Diagnostic, Therapeutic, and Theranostic Multifunctional Microneedles DOI
Yavuz Nuri Ertaş,

Derya Ertas,

Ahmet Erdem

et al.

Small, Journal Year: 2024, Volume and Issue: 20(26)

Published: Feb. 22, 2024

Abstract Microneedles (MNs) have maintained their popularity in therapeutic and diagnostic medical applications throughout the past decade. MNs are originally designed to gently puncture stratum corneum layer of skin lately evolved into intelligent devices with functions including bodily fluid extraction, biosensing, drug administration. offer limited invasiveness, ease application, minimal discomfort. Initially manufactured solely from metals, now available polymer‐based varieties. can be used create systems that deliver drugs chemicals uniformly, collect fluids, stimulus‐sensitive. Although these advancements favorable terms biocompatibility production costs, they insufficient for use MNs. This is first comprehensive review discusses individual MN toward evolution development smart multifunctional a variety novel impactful future applications. The study examines fabrication techniques, application purposes, experimental details constructs perform multiple concurrently, sensing, drug‐molecule release, sampling, remote communication capabilities. It highly likely near future, MN‐based will useful important component standard practice different

Language: Английский

Citations

15
Extracellular Vesicles: A New Star for Gene Drug Delivery DOI Creative Commons

Man Sun,

Huan Zhang, Jiayi Liu

et al.

International Journal of Nanomedicine, Journal Year: 2024, Volume and Issue: Volume 19, P. 2241 - 2264

Published: March 1, 2024

Abstract: Recently, gene therapy has become a subject of considerable research and been widely evaluated in various disease models. Though it is considered as stand-alone agent for COVID-19 vaccination, still suffering from the following drawbacks during its translation bench to bedside: high sensitivity exogenous nucleic acids enzymatic degradation; severe side effects induced either by or components formulation; difficulty cross barriers before reaching therapeutic target. Therefore, successful application therapy, safe reliable transport vector urgently needed. Extracellular vesicles (EVs) are ideal candidate delivery drugs owing their low immunogenicity, good biocompatibility toxicity. To better understand properties EVs advantages drug vehicles, this review covers origin methods generation, well common isolation purification research, with pros cons discussed. Meanwhile, engineering also highlighted. In addition, paper presents progress EVs-mediated microRNAs, small interfering RNAs, messenger plasmids, antisense oligonucleotides. We believe will provide theoretical basis development drugs. Keywords: extracellular vesicles, system,

Language: Английский

Citations

12
Genetically engineered loaded extracellular vesicles for drug delivery DOI

Zuriñe Erana-Perez,

Manoli Igartúa, Edorta Santos‐Vizcaíno

et al.

Trends in Pharmacological Sciences, Journal Year: 2024, Volume and Issue: 45(4), P. 350 - 365

Published: March 19, 2024

Language: Английский

Citations

11
Hydrogels loaded with MSC‐derived small extracellular vesicles: A novel cell‐free tissue engineering system for diabetic wound management DOI Creative Commons
Weicheng Zhong,

Hao Meng,

Liqian Ma

et al.

View, Journal Year: 2024, Volume and Issue: 5(4)

Published: July 18, 2024

Abstract With the aging and obesity era, increasing incidence of diabetes diabetic complications, especially non‐healing wounds, imposes a serious economic burden on both patients society. The complex microenvironments, including hyperglycemia, bacterial infection, ischemia, nerve damage, lead to prolonged inflammation proliferation phase wounds. Mesenchymal stem cell‐derived small extracellular vesicles (MSC‐sEVs), which contain rich variety therapeutic molecules, have been chased for decades because their potential roles in cellular communication, tissue regeneration, drug delivery. As powerful tools controlled‐sustained release sEVs, biocompatible hydrogels applied wide range biomedical applications. Herein, we first summarize pathological features such as angiopathy, neuropathy, immune cell dysfunction. Then, discuss biological properties, performance, stability pure MSC‐sEVs. After that, components, application patterns, responsiveness hydrogels. Next, loading avenues MSC‐sEVs into hydrogel, behaviors sEVs from hydrogels, influence crosslinking method hydrogel‐sEV composites. Finally, provide an overview current applications loaded with novel cell‐free engineering system managing wounds propose critical unsolved issues. This review is expected meaningful guidance developing wound management.

Language: Английский

Citations

10