Biomaterials, Journal Year: 2024, Volume and Issue: 314, P. 122853 - 122853
Published: Sept. 27, 2024
Language: Английский
Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)
Published: July 5, 2024
Abstract Fully targeted mRNA therapeutics necessitate simultaneous organ-specific accumulation and effective translation. Despite some progress, delivery systems are still unable to fully achieve this. Here, we reformulate lipid nanoparticles (LNPs) through adjustments in material structures compositions systematically the pulmonary hepatic (respectively) distribution expression. A combinatorial library of degradable-core based ionizable cationic lipids is designed, following by optimisation LNP compositions. Contrary current paradigms, our findings demonstrate that cholesterol phospholipid dispensable for functionality. Specifically, cholesterol-removal addresses persistent challenge preventing nanoparticle tissues. By modulating simplifying intrinsic components, concurrent translation achieved lung liver, respectively. This targeting strategy applicable existing with potential expand progress precise therapy diverse diseases.
Language: Английский
Citations
38
International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(18), P. 10166 - 10166
Published: Sept. 22, 2024
Lipid nanoparticles (LNPs) have emerged as leading non-viral carriers for messenger RNA (mRNA) delivery in clinical applications. Overcoming challenges safe and effective mRNA to target tissues cells, along with controlling release from the vehicle, remains pivotal mRNA-based therapies. This review elucidates structure of LNPs, mechanism delivery, targeted LNPs various cells tissues, including leukocytes, T-cells, dendritic Kupffer hepatic endothelial extrahepatic tissues. Here, we discuss applications mRNA-LNP vaccines prevention infectious diseases treatment cancer genetic diseases. Although remain terms efficiency, specific tissue targeting, toxicity, storage stability, technology holds extensive potential
Language: Английский
Citations
14
Vaccines, Journal Year: 2024, Volume and Issue: 12(10), P. 1148 - 1148
Published: Oct. 8, 2024
The advent of lipid nanoparticles (LNPs) as a delivery platform for mRNA therapeutics has revolutionized the biomedical field, particularly in treating infectious diseases, cancer, genetic disorders, and metabolic diseases. Recent Advances Therapeutic LNPs: LNPs, composed ionizable lipids, phospholipids, cholesterol, polyethylene glycol (PEG) facilitate efficient cellular uptake cytosolic release while mitigating degradation by nucleases. However, synthetic entities, LNPs face challenges that alter their therapeutic efficacy safety concerns. Toxicity/Reactogenicity/Immunogenicity: This review provides comprehensive overview latest advancements LNP research, focusing on preclinical assessments encompassing toxicity, reactogenicity, immunogenicity. Summary Outlook: Additionally, it outlines potential strategies addressing these offers insights into future research directions enhancing application therapeutics.
Language: Английский
Citations
11
ACS Applied Materials & Interfaces, Journal Year: 2024, Volume and Issue: 16(20), P. 25698 - 25709
Published: May 8, 2024
Much of current clinical interest has focused on mRNA therapeutics for the treatment lung-associated diseases, such as infections, genetic disorders, and cancers. However, safe efficient delivery to lungs, especially different pulmonary cell types, is still a formidable challenge. In this paper, we proposed cationic lipid pair (CLP) strategy, which utilized liver-targeted ionizable its derived quaternary ammonium CLP improve liver-to-lung tropism four-component nanoparticles (LNPs) in vivo delivery. Interestingly, structure–activity investigation identified that using lipids with higher performance their counterparts optimal design improving lung-targeted The strategy was also verified be universal suitable clinically available SM-102 ALC-0315 develop LNP systems. Moreover, demonstrated CLP-based LNPs were exhibited potent transfection endothelial epithelial cells. As result, provided powerful shifting preference from liver exhibiting great potential broadening application scenario mRNA-based therapy.
Language: Английский
Citations
7
Vaccines, Journal Year: 2024, Volume and Issue: 12(8), P. 873 - 873
Published: Aug. 1, 2024
mRNA vaccines are leading a medical revolution. technologies utilize the host's own cells as bio-factories to produce proteins that serve antigens. This revolutionary approach circumvents complicated processes involved in traditional vaccine production and empowers with ability respond emerging or mutated infectious diseases rapidly. Additionally, robust cellular immune response elicited by has shown significant promise cancer treatment. However, inherent instability of complexity tumor immunity have limited its broader application. Although emergence pseudouridine ionizable cationic lipid nanoparticles (LNPs) made clinical application possible, there remains substantial potential for further improvement immunogenicity delivered antigens preventive therapeutic effects technology. Here, we review latest advancements vaccines, including but not target selection delivery systems. offers multifaceted perspective on this rapidly evolving field.
Language: Английский
Citations
7
Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)
Published: June 28, 2024
Abstract Lipid nanoparticles (LNPs) have proven themselves as transformative actors in chimeric antigen receptor (CAR) T cell therapy, surpassing traditional methods and addressing challenges like immunogenicity, reduced toxicity, improved safety. Promising preclinical results signal a shift toward safer more effective CAR treatments. Ongoing research aims to validate these findings clinical trials, marking new era guided by LNPs utility therapy. Herein, we explore the preference for over methods, highlighting versatility of their delivery nucleic acids. Additionally, address key considerations, heralding Graphical
Language: Английский
Citations
6
BMEMat, Journal Year: 2024, Volume and Issue: unknown
Published: Sept. 19, 2024
Abstract mRNA therapeutics have significantly evolved within the life sciences, particularly in applications such as vaccines, tumor immunotherapy, protein replacement, gene editing, and monoclonal antibody therapy. To fully realize potential of drugs mitigate adverse effects, substantial vector materials been developed for delivery these pharmaceutical agents. Lipid nanoparticles (LNPs) represent most clinically advanced carriers, recognized by U.S. Food Drug Administration approved vaccines numerous clinical trials. Diverse therapeutic necessitate tailored design LNPs. Herein, we outline principles LNP delivery, focusing specifically on their effectiveness, targeting capabilities, safety profiles, nanoparticle stability. Additionally, present latest advancements mRNA‐LNP technology. This review aims to elucidate benefits systems therapeutics, providing insights into breakthroughs innovative ideas further enhancing advantages. These summaries are dedicated promoting broader LNP‐mRNA drugs, aiming advance treatment serious diseases an effective safe manner.
Language: Английский
Citations
5
Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)
Published: Nov. 14, 2024
RNA therapeutics, such as mRNA, siRNA, and CRISPR–Cas9, present exciting avenues for treating diverse diseases. However, their potential is commonly hindered by vulnerability to degradation poor cellular uptake, requiring effective delivery systems. Lipid nanoparticles (LNPs) have emerged a leading choice in vivo delivery, offering protection against degradation, enhanced facilitation of endosomal escape. LNPs encounter numerous challenges targeted vivo, demanding advanced particle engineering, surface functionalization with targeting ligands, profound comprehension the biological milieu which they function. This review explores structural physicochemical characteristics LNPs, in-vivo fate, customization therapeutics. We highlight quality-by-design (QbD) approach beyond liver, focusing on biodistribution, immunogenicity, toxicity. In addition, we explored current strategies associated ensuring repeated-dose efficacy, safety, tissue-specific gene delivery. Furthermore, provide insights into clinical applications various classes diseases finally prospects
Language: Английский
Citations
5
Nature Biomedical Engineering, Journal Year: 2025, Volume and Issue: unknown
Published: March 28, 2025
Language: Английский
Citations
0
Advanced Functional Materials, Journal Year: 2025, Volume and Issue: unknown
Published: March 30, 2025
Abstract Intracerebral hemorrhage (ICH) causes uncontrolled neuroinflammation/oxidative stress to aggravate secondary brain injury (SBI) for high mortality and disability but lacks effective pharmacotherapy in clinical practices. This represents an imperative need discover potential targets develop advanced therapeutic strategies. Herein, it is discovered that cell‐free DNA (cfDNA, a driving factor of inflammation) level serum positively correlates with SBI severity speculated as targeting molecule. However, traditional cfDNA‐scavenging materials are mainly limited within the polycationic type exist severe side effects. this work designs drug delivery nanosystem, which utilizes pathogenesis‐activated sequential disassembly‐reassembly process situ dual‐scavenge cfDNA ROS regulation stress, thereby reducing preventing further damage experimental mice. The findings not only demonstrate importance also provide enhance toward alleviation on following ICH.
Language: Английский
Citations
0