3D Multispheroid Assembly Strategies towards Tissue Engineering and Disease Modeling

Advanced Healthcare Materials, Journal Year: 2024, Volume and Issue: unknown

Published: June 25, 2024

Abstract Cell spheroids (esp. organoids) as 3D culture platforms are popular models for representing cell–cell and cell–extracellular matrix (ECM) interactions, bridging the gap between 2D cell cultures natural tissues. with spatially organized multiple types preferred gaining comprehensive insights into tissue pathophysiology constructing in vitro tissues disease because of complexities In recent years, an assembly strategy using (or living building blocks has been developed to construct complex spatial organization. Here, a overview advances multispheroid studies is provided. The different mechanisms techniques, i.e., automated directed assembly, noncontact remote programmed self‐assembly, introduced. processing steps, advantages, technical limitations existing methodologies summarized. Applications strategies modeling, drug screening, engineering, organogenesis reviewed. Finally, this review concludes by emphasizing persistent issues future perspectives, encouraging researchers adopt techniques generating advanced that better resemble real

Language: Английский

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Rational design and modular synthesis of biodegradable ionizable lipids via the Passerini reaction for mRNA delivery

Proceedings of the National Academy of Sciences, Journal Year: 2025, Volume and Issue: 122(5)

Published: Jan. 30, 2025

The ionizable lipid component of nanoparticle (LNP) formulations is essential for mRNA delivery by facilitating endosomal escape. Conventionally, these lipids are synthesized through complex, multistep chemical processes that both time-consuming and require significant engineering. Furthermore, the development new hindered a limited understanding structure-activity relationships effective delivery. In this work, we have developed modular platform utilizing Passerini reaction to rapidly generate large, chemically diverse libraries biodegradable lipids. This high-throughput approach enables systematic exploration various components–head groups, tails, spacers–and their impacts on efficiency. By investigating hydrogen bonding potential between lipid’s head groups mRNA’s ribose phosphate found optimizing methylene units linkages could enhance escape and, consequently, efficiencies. Leveraging insight, our has led identification A4B4-S3, which outperforms current clinical benchmark, SM-102, in gene editing efficacy mouse liver following systemic administration demonstrates promise repeat-dose protein replacement treatments. work not only offers rapid, scalable method synthesis but also deepens relationships, paving way more therapeutics.

Language: Английский

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The potential of mRNA vaccines in cancer nanomedicine and immunotherapy

Trends in Immunology, Journal Year: 2023, Volume and Issue: 45(1), P. 20 - 31

Published: Dec. 22, 2023

Language: Английский

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Optimizing mRNA-Loaded Lipid Nanoparticles as a Potential Tool for Protein-Replacement Therapy

Pharmaceutics, Journal Year: 2024, Volume and Issue: 16(6), P. 771 - 771

Published: June 6, 2024

Lipid nanoparticles (LNPs) tailored for mRNA delivery were optimized to serve as a platform treating metabolic diseases. Four distinct lipid mixes (LMs) formulated by modifying various components: LM1 (ALC-0315/DSPC/Cholesterol/ALC-0159), LM2 (ALC-0315/DOPE/Cholesterol/ALC-0159), LM3 (ALC-0315/DSPC/Cholesterol/DMG-PEG2k), and LM4 (DLin-MC3-DMA/DSPC/Cholesterol/ALC-0159). LNPs exhibited stability homogeneity with mean size of 75 90 nm, confirmed cryo-TEM SAXS studies. High encapsulation (95–100%) was achieved. effectively delivered EGFP-encoding HepG2 DC2.4 cell lines. induced cytokine secretion from human peripheral blood mononuclear cells (PBMCs), revealing that LM1, LM2, 1.5- 4-fold increases in IL-8, TNF-α, MCP-1 levels, while showed minimal changes. Reporter expression observed LNP-treated PBMCs. Hemotoxicity studies formulation biocompatibility values below 2%. In vivo biodistribution mice post intramuscular injection significant expression, mainly the liver. The modification LNP components influenced reactogenicity, inflammatory response, offering promising selecting less reactogenic carriers suitable repetitive dosing disease treatment.

Language: Английский

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A Nanoparticle Vaccine Displaying Conserved Epitopes of the Preexisting Neutralizing Antibody Confers Broad Protection against SARS-CoV-2 Variants

ACS Nano, Journal Year: 2024, Volume and Issue: 18(27), P. 17749 - 17763

Published: June 27, 2024

The rapid development of the SARS-CoV-2 vaccine has been used to prevent spread coronavirus 2019 (COVID-19). However, ongoing and future pandemics caused by variants mutations underscore need for effective vaccines that provide broad-spectrum protection. Here, we developed a nanoparticle with broad protection against divergent variants. corresponding conserved epitopes preexisting neutralizing (CePn) antibody were presented on self-assembling Helicobacter pylori ferritin generate CePnF nanoparticle. Intranasal immunization mice nanoparticles induced robust humoral, cellular, mucosal immune responses long-lasting immunity. CePnF-induced antibodies exhibited cross-reactivity activity different coronaviruses (CoVs). vaccination significantly inhibited replication pathology Delta, WIV04, Omicron strains in hACE2 transgenic and, thus, conferred these Our constructed nanovaccine targeting can serve as promising candidate universal vaccine.

Language: Английский

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