Food Research International, Год журнала: 2025, Номер unknown, С. 116315 - 116315
Опубликована: Март 1, 2025
Язык: Английский
Vaccines, Год журнала: 2024, Номер 12(10), С. 1148 - 1148
Опубликована: Окт. 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.
Язык: Английский
Процитировано
24
Nature Biotechnology, Год журнала: 2024, Номер unknown
Опубликована: Окт. 16, 2024
Язык: Английский
Процитировано
20
Nature Materials, Год журнала: 2025, Номер unknown
Опубликована: Фев. 28, 2025
Язык: Английский
Процитировано
5
ACS Nano, Год журнала: 2025, Номер unknown
Опубликована: Янв. 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.
Язык: Английский
Процитировано
4
Nature Communications, Год журнала: 2025, Номер 16(1)
Опубликована: Янв. 14, 2025
Abstract Amidst the rising prevalence of respiratory diseases, importance effective lung treatment modalities is more critical than ever. However, current drug delivery systems face significant limitations that impede their efficacy and therapeutic outcome. Biohybrid microrobots have shown considerable promise for active in vivo delivery, especially pulmonary applications via intratracheal routes. invasive nature administration poses barriers to its clinical translation. Herein, we report on an efficient non-invasive inhalation-based method delivering lungs. A nebulizer employed encapsulate picoeukaryote algae within small aerosol particles, enabling them reach lower tract. Post nebulization, retain motility (~55 μm s -1 ) help achieve a homogeneous distribution long-term retention exceeding five days Therapeutic demonstrated mouse model acute methicillin-resistant Staphylococcus aureus pneumonia using this inhalation approach deliver functionalized with platelet membrane-coated polymeric nanoparticles loaded vancomycin. These promising findings underscore benefits inhalable biohybrid setting does not require anesthesia, highlighting substantial translational potential system routine applications.
Язык: Английский
Процитировано
3
ACS Nano, Год журнала: 2025, Номер unknown
Опубликована: Фев. 17, 2025
Messenger RNA (mRNA) encoding base editors, along with single guide RNAs (sgRNAs), have emerged as a promising therapeutic approach for various disorders. However, there is still insufficient exploration in achieving targeted and efficient delivery of mRNA sgRNA to multiple organs while ensuring high biocompatibility stability vivo. To address this challenge, we synthesized library 108 poly(β-amino) esters (PBAEs) by incorporating 100% hydrophobic side chains end-caps varying amines. These PBAEs were further formulated other excipients, including helper lipids, cholesterol, PEGylated form polymer–lipid nanoparticles (PLNPs). Structure–function analysis revealed that eLog P could serve predictive parameter determining the liver or lung tropism PLNPs. The end-capped monoamines was significantly higher compared those diamines. Leveraging these findings, expanded PBAE identified leading (7C8C8) efficiency outperforming current FDA-approved ionizable lipids (ALC-0315, SM-102, Dlin-MC3-DMA). LD50 empty PLNPs determined be 403.8 ± 49.46 mg/kg, indicating safety profile. Additionally, demonstrated sustained transfection activity at least 2 months when stored −20 °C after freezing 4 following lyophilization. Subsequently, vivo editing using achieved an impressive approximately 70% significant reduction protein levels exceeding 90%. Notably, synergistic effects observed through simultaneous disruption proprotein convertase subtilisin/kexin type 9 angiopoietin-like 3 genes, resulting low-density lipoprotein cholesterol over 60% several months. compelling findings provide strong support development platforms mRNA-based therapies.
Язык: Английский
Процитировано
2
Stem Cell Research & Therapy, Год журнала: 2025, Номер 16(1)
Опубликована: Янв. 29, 2025
Chronic pulmonary diseases pose a prominent health threat globally owing to their intricate pathogenesis and lack of effective reversal therapies. Nowadays, lung transplantation stands out as feasible treatment option for patients with end-stage disease. Unfortunately, the use this is limited by donor organ shortage severe immunological rejection reactions. Recently, airway basal stem cells (BSCs) have emerged novel therapeutic strategy in regenerative medicine because substantial potential repairing structure function. Airway BSCs, which are strongly capable self-renewal multi-lineage differentiation, can effectively attenuate epithelial injury caused environmental factors or genetic disorders, such cystic fibrosis. This review comprehensively explores efficacy action mechanisms BSCs across various disease models describes strategies inducing pluripotent differentiate into lineages on basis original research findings. Additionally, also discusses technical biological challenges translating these findings clinical applications offers prospective views future directions, therefore broadening landscape medicine.
Язык: Английский
Процитировано
1
Advanced Materials, Год журнала: 2025, Номер unknown
Опубликована: Фев. 9, 2025
Lipid nanoparticles (LNPs) with highly efficient and specific extrahepatic targeting abilities are promising in gene delivery, the lipopeptides (LPs) excellent designability functionality expected to empower construction of functional LNPs. This study aims develop ionizable components that accurately match different lipid systems through modular design LPs. Based on this, a lipopeptide-based organ-specific (POST) LNP screening strategy is constructed, which lysine-histidine-based (KH-LPs) designed as components. The optimal KH-LP screened vitro shows siRNA/mRNA transfecting ability various hard-to-transfect cell lines. Compared classic LNPs, POST LNPs vivo achieve even higher (or at least comparable) efficiency specificity delivering mRNA siRNA lung, liver, spleen, respectively. structure-activity relationship (SAR) proves regulation LP structures can provide for systems, demonstrating potential this developing selective open up more possibilities therapy.
Язык: Английский
Процитировано
1
Nature Biotechnology, Год журнала: 2024, Номер unknown
Опубликована: Ноя. 13, 2024
Abstract Engineered virus-like particles (eVLPs) are promising vehicles for transient delivery of proteins and RNAs, including gene editing agents. We report a system the laboratory evolution eVLPs that enables discovery eVLP variants with improved properties. The uses barcoded guide RNAs loaded within DNA-free eVLP-packaged cargos to uniquely label each variant in library, enabling identification desired following selections applied this mutate select capsids production properties or transduction efficiencies human cells. By combining beneficial capsid mutations, we developed fifth-generation (v5) eVLPs, which exhibit 2–4-fold increase cultured mammalian cell potency compared previous-best v4 eVLPs. Analyses v5 suggest these mutations optimize packaging ribonucleoprotein rather than native viral genomes substantially alter structure. These findings potential support development
Язык: Английский
Процитировано
8
Journal of Nanobiotechnology, Год журнала: 2024, Номер 22(1)
Опубликована: Ноя. 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
Язык: Английский
Процитировано
8