Dual-Targeting of PDPN-Expressing Synovial Fibroblasts and Macrophages via CLEC-2-Engineered Exosomes for Osteoarthritis Therapy DOI Creative Commons
Bo Yu,

Rui Peng,

Zitao Liu

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 6, 2024

Abstract Synovitis is often associated with osteoarthritis (OA) and may even precede the onset of OA symptoms. Although targeting synovial inflammation has shown therapeutic promise in OA, synovium's heterogeneous composition, multiple cell types contributing to inflammatory response, indicates that focusing on a single population not provide most favorable results. This investigation employed scRNA-seq tissues from both human murine sources, revealing fibroblasts macrophages expressing high levels Podoplanin (PDPN). These cells constitute approximately 70% total display pro-inflammatory properties. Drawing inspiration unique interaction between PDPN CLEC-2, we engineered mesenchymal stromal cell-derived exosomes overexpress CLEC-2 (ExosomeCLEC-2) encapsulated liquiritigenin-loaded poly (lactic-co-glycolic acid) (PLGA) within ExosomeCLEC-2 membrane (EMCLEC-2), creating PDPN-targeting nanoparticle system called EMCLEC-2-PLGA-liquiritigenin (EMPL). Remarkably, EMPL concurrently targets PDPNhigh macrophages, exhibiting anti-inflammatory effects both vitro in vivo, preventing cartilage degeneration traumatic model. In summary, our research highlights potential developing platform can target mitigate processes offering novel promising strategy for treatment osteoarthritis.

Language: Английский

Emerging Delivery Systems for Enabling Precision Nucleic Acid Therapeutics DOI

Xiaochun Bian,

Liping Zhou,

Zhiwei Luo

et al.

ACS Nano, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 21, 2025

Nucleic acid therapeutics represent a highly promising treatment approach in modern medicine, treating diseases at the genetic level. However, these face numerous challenges practical applications, particularly regarding their stability, effectiveness, cellular uptake efficiency, and limitations delivering them specifically to target tissues. To overcome obstacles, researchers have developed various innovative delivery systems, including viral vectors, lipid nanoparticles, polymer inorganic protein carriers, exosomes, antibody oligonucleotide conjugates, DNA nanostructure-based systems. These systems enhance therapeutic efficacy of nucleic drugs by improving targeting specificity, half-life vivo. In this review, we systematically discuss different types drugs, analyze major barriers encountered delivery, summarize current research progress emerging We also highlight latest advancements application for diseases, infectious cancer, brain wound healing. This review aims provide comprehensive overview drug systems' status future directions integrating nanotechnology, biomaterials science, gene editing technologies, emphasizing transformative potential precision medicine.

Language: Английский

Citations

2
Exploring precision treatments in immune‐mediated inflammatory diseases: Harnessing the infinite potential of nucleic acid delivery DOI Creative Commons
Lingxiao Xu, Z. Shao, Xia Fang

et al.

Exploration, Journal Year: 2024, Volume and Issue: unknown

Published: May 24, 2024

Immune-mediated inflammatory diseases (IMIDs) impose an immeasurable burden on individuals and society. While the conventional use of immunosuppressants disease-modifying drugs has provided partial relief control, their inevitable side effects limited efficacy cast a shadow over finding cure. Promising nucleic acid have shown potential to exert precise at molecular level, with different classes acids having regulatory functions through varying mechanisms. For better delivery acids, safe effective viral vectors non-viral systems (including liposomes, polymers, etc.) been intensively explored. Herein, after describing range categories vectors, we focus application therapeutic in various IMIDs, including rheumatoid arthritis, bowel disease, psoriasis, multiple sclerosis, asthma, ankylosing spondylitis, systemic lupus erythematosus, uveitis. Molecules implicated inflammation immune dysregulation are abnormally expressed series meticulous modulation therapy results degrees remission improvement these diseases. By synthesizing findings centered specific targets, this review delivers systematic elucidation perspective towards advancing utilization therapeutics for managing IMIDs.

Language: Английский

Citations

10
L-carnitine modified nanoparticles target the OCTN2 transporter to improve the oral absorption of jujuboside B DOI
Wei Li, Yanqing Zhang, Jing Zhao

et al.

European Journal of Pharmaceutics and Biopharmaceutics, Journal Year: 2024, Volume and Issue: 196, P. 114185 - 114185

Published: Jan. 26, 2024

Language: Английский

Citations

9
The hidden messengers: cancer associated fibroblasts—derived exosomal miRNAs as key regulators of cancer malignancy DOI Creative Commons
Zixuan Gou, Jiannan Li, Jianming Liu

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2024, Volume and Issue: 12

Published: April 17, 2024

Cancer-associated fibroblasts (CAFs), a class of stromal cells in the tumor microenvironment (TME), play key role controlling cancer cell invasion and metastasis, immune evasion, angiogenesis, resistance to chemotherapy. CAFs mediate their activities by secreting soluble chemicals, releasing exosomes, altering extracellular matrix (ECM). Exosomes contain various biomolecules, such as nucleic acids, lipids, proteins. microRNA (miRNA), 22–26 nucleotide non-coding RNA, can regulate cellular transcription processes. Studies have shown that miRNA-loaded exosomes secreted engage regulatory communication networks with other TME constituents. This study focused on roles CAF-derived exosomal miRNAs generating malignant characteristics, including modulation, growth, migration invasion, epithelial-mesenchymal transition (EMT), treatment resistance. thoroughly examines miRNA’s dual promoting suppressing cancer. Thus, changes be used biomarkers for diagnosis prognosis patients, specificity develop newer therapies. review also discusses pressing problems require immediate attention, aiming inspire researchers explore more novel avenues this field.

Language: Английский

Citations

9
Innovating intervertebral disc degeneration therapy: Harnessing the power of extracellular vesicles DOI Creative Commons
Shanfeng Chen,

Yiming Dou,

Yiming Zhang

et al.

Journal of Orthopaedic Translation, Journal Year: 2025, Volume and Issue: 50, P. 44 - 55

Published: Jan. 1, 2025

Language: Английский

Citations

1
RNA nanotherapeutics for hepatocellular carcinoma treatment DOI
Yihang Yuan, Weijie Sun, Jiaqi Xie

et al.

Theranostics, Journal Year: 2024, Volume and Issue: 15(3), P. 965 - 992

Published: Dec. 2, 2024

Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality worldwide, particularly due to the limited effectiveness current therapeutic options for advanced-stage disease. The efficacy traditional treatments is often compromised by intricate liver microenvironment and inherent heterogeneity. RNA-based therapeutics offer promising alternative, utilizing innovative approach targeting aberrant molecular pathways modulating tumor microenvironment. integration nanotechnology in this field, through development advanced nanocarrier delivery systems, especially lipid nanoparticles (LNPs), polymer (PNPs), bioinspired vectors, enhances precision RNA therapies. This review highlights significant progress nanotherapeutics HCC treatment, covering micro (miRNA), small interfering (siRNA), message (mRNA), activating (saRNA) mediated gene silencing, protein restoration, activation, cancer vaccines, concurrent therapy. It further comprehensively discusses prevailing challenges within landscape provides forward-looking perspective on potential transform treatment.

Language: Английский

Citations

5
Revival of Bioengineered Proteins as Carriers for Nucleic Acids DOI Creative Commons

David C. Scherer,

Michael Burger, Jean‐Christophe Leroux

et al.

Bioconjugate Chemistry, Journal Year: 2024, Volume and Issue: 35(5), P. 561 - 566

Published: April 15, 2024

ADVERTISEMENT RETURN TO ARTICLES ASAPViewpointNEXTRevival of Bioengineered Proteins as Carriers for Nucleic AcidsDavid SchererDavid SchererInstitute Pharmaceutical Sciences, Department Chemistry and Applied Biosciences, ETH Zurich, Zurich 8093, SwitzerlandMore by David Scherer, Michael Burger*Michael BurgerInstitute Switzerland*[email protected]More Burger, Jean-Christophe Leroux*Jean-Christophe LerouxInstitute Lerouxhttps://orcid.org/0000-0001-5601-1292Cite this: Bioconjugate Chem. 2024, XXXX, XXX, XXX-XXXPublication Date (Web):April 15, 2024Publication History Received22 February 2024Accepted1 April 2024Published online15 2024https://doi.org/10.1021/acs.bioconjchem.4c00079© 2024 The Authors. Published American Chemical Society. This publication is licensed under CC-BY 4.0. License Summary*You are free to share (copy redistribute) this article in any medium or format adapt (remix, transform, build upon) the material purpose, even commercially within parameters below:Creative Commons (CC): a Creative license.Attribution (BY): Credit must be given creator.View full license*DisclaimerThis summary highlights only some key features terms actual license. It not license has no legal value. Carefully review before using these materials. Open Access indicated. Learn MoreArticle Views-Altmetric-Citations-LEARN ABOUT THESE METRICSArticle Views COUNTER-compliant sum text downloads since November 2008 (both PDF HTML) across all institutions individuals. These metrics regularly updated reflect usage leading up last few days.Citations number other articles citing article, calculated Crossref daily. Find more information about citation counts.The Altmetric Attention Score quantitative measure attention that research received online. Clicking on donut icon will load page at altmetric.com with additional details score social media presence article. how calculated. Share Add toView InAdd Full Text ReferenceAdd Description ExportRISCitationCitation abstractCitation referencesMore Options onFacebookTwitterWechatLinked InRedditEmail (2 MB) Get e-AlertscloseSUBJECTS:Endosomal escape,Gene delivery,Genetics,Nucleic acids,Peptides proteins e-Alerts

Language: Английский

Citations

4
Hydrogen Sulfide‐Triggered Artificial DNAzyme Switches for Precise Manipulation of Cellular Functions DOI
Xuan Xie,

Hexin Nan,

Jialong Peng

et al.

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(49)

Published: Sept. 27, 2024

Abstract The development of synthetic molecular tools responsive to biological cues is crucial for advancing targeted cellular regulation. A significant challenge the regulation processes in response gaseous signaling molecules such as hydrogen sulfide (H 2 S). To address this, we present design Gas molecule‐Responsive Artificial DNAzyme‐based Switches (GRAS) manipulate functions via H S‐sensitive DNAzymes. By incorporating stimuli‐responsive moieties phosphorothioate backbone, DNAzymes are strategically designed with S‐responsive azide groups at cofactor binding locations within catalytic core region. These modifications enable their activation through S‐reducing decaging, thereby initiating substrate cleavage activity. Our approach allows flexible customization various regulate distinct diverse scenarios. Intracellularly, enzymatic activity GRAS promotes S‐induced specific mRNA sequences, enabling gene silencing and inducing apoptosis cancer cells. Moreover, integrating dynamic DNA assembly grafting these functional switches onto cell surface receptors, facilitating S‐triggered receptor dimerization. This extracellular transmits signals intracellularly behaviors migration proliferation. Collectively, capable rewiring cues, offering a promising avenue advanced engineering.

Language: Английский

Citations

4
Gene therapy for chronic pain management DOI Creative Commons
Yize Li, Ru‐Rong Ji

Cell Reports Medicine, Journal Year: 2024, Volume and Issue: unknown, P. 101756 - 101756

Published: Oct. 1, 2024

Language: Английский

Citations

4
Potential and development of cellular vesicle vaccines in cancer immunotherapy DOI Creative Commons

Wenxi Zhao,

Xianjun Li,

Jialu Guan

et al.

Discover Oncology, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 15, 2025

Cancer vaccines are promising as an effective means of stimulating the immune system to clear tumors well establish surveillance. In this paper, we discuss main platforms and current status cancer propose a new vaccine platform, cytosolic vesicle vaccine. This has unique structure that can integrate antigen adjuvant carriers improve delivery efficiency activation ability, which brings ideas for design. Tumor exosomes carry antigens MHC-peptide complexes, provide tumor antigen-processing cells increase chances recognition by cells. DEVs play role in amplifying response acting dissemination antigenic substances dendritic OMVs, with their natural properties, one advantages preparation antitumor vaccines. paper presents these three bacteria/extracellular vesicles discusses potential applications functionally modified extracellular after cellular engineering or genetic engineering, clinical trials summary, direction research.

Language: Английский

Citations

0