Nanoscale, Journal Year: 2024, Volume and Issue: 16(14), P. 6820 - 6836
Published: Jan. 1, 2024
This review highlights the latest advances in lipid nanoparticle mRNA based nanomedicines under preclinical and clinical investigation.
Language: Английский
Advanced Materials, Journal Year: 2023, Volume and Issue: 35(51)
Published: May 17, 2023
Abstract Messenger RNA (mRNA) has received great attention in the prevention and treatment of various diseases due to success coronavirus disease 2019 (COVID‐19) mRNA vaccines (Comirnaty Spikevax). To meet therapeutic purpose, it is required that must enter target cells express sufficient proteins. Therefore, development effective delivery systems necessary crucial. Lipid nanoparticle (LNP) represents a remarkable vehicle indeed accelerated applications humans, as several mRNA‐based therapies have already been approved or are clinical trials. In this review, focus on mRNA‐LNP‐mediated anticancer therapy. It summarizes main strategies mRNA‐LNP formulations, discusses representative approaches cancer, points out current challenges possible future directions research field. hoped these delivered messages can help further improve application technology cancer
Language: Английский
Citations
180
Vaccines, Journal Year: 2023, Volume and Issue: 11(3), P. 658 - 658
Published: March 14, 2023
Lipid nanoparticles (LNPs) have recently emerged as one of the most advanced technologies for highly efficient in vivo delivery exogenous mRNA, particularly COVID-19 vaccine delivery. LNPs comprise four different lipids: ionizable lipids, helper or neutral cholesterol, and lipids attached to polyethylene glycol (PEG). In this review, we present recent advances insights design LNPs, well their composition properties, with a subsequent discussion on development vaccines. particular, are critical drivers complexing mRNA delivery, role vaccines is discussed detail. Furthermore, use effective vehicles vaccination, genome editing, protein replacement therapy explained. Finally, expert opinion discussed, which may address future challenges developing using based novel set lipids. Developing systems improved safety against some severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants remains difficult.
Language: Английский
Citations
64
Advanced Science, Journal Year: 2023, Volume and Issue: 10(19)
Published: April 24, 2023
Ionizable lipid-based nanoparticles (LNPs) are the most advanced non-viral drug delivery systems for RNA therapeutics and vaccines. However, cell type-specific, extrahepatic mRNA is still a major hurdle, hampering development of novel therapeutic modalities. Herein, ionizable lipid library synthesized by modifying hydrophobic tail chains linkers. Combined with other helper lipids utilizing microfluidic mixing approach, stable LNPs formed. Using Luciferase-mRNA, mCherry mRNA, Cre together TdTomato animal model, superior forming potent cell-type specific identified. In vitro assays concluded that combining branched ester hydroxylamine linker negatively affects efficiency. vivo studies identify Lipid 23 as liver-trophic, 16 type-specific CD11bhi macrophage population without an additional targeting moiety. Finally, in efficiency toxicity these compared SM-102-based LNP (Moderna's formulation) shown to be cell-specific LNPs. Overall, this study suggests structural combination can drive functionality vivo.
Language: Английский
Citations
53
Advanced Materials, Journal Year: 2023, Volume and Issue: unknown
Published: Oct. 4, 2023
Abstract Lipid‐based nanoparticles (LBNPs) are currently the most promising vehicles for nucleic acid drug (NAD) delivery. Although their clinical applications have achieved success, NAD delivery efficiency and safety still unsatisfactory, which are, to a large extent, due existence of multi‐level physiological barriers in vivo. It is important elucidate interactions between these LBNPs, will guide more rational design efficient with low adverse effects facilitate broader therapeutics. This review describes obstacles challenges biological at systemic, organ, sub‐organ, cellular, subcellular levels. The strategies overcome comprehensively reviewed, mainly including physically/chemically engineering LBNPs directly modifying by auxiliary treatments. Then potentials successful translation preclinical studies into clinic discussed. In end, forward look on manipulating protein corona (PC) addressed, may pull off trick overcoming those significantly improve efficacy LBNP‐based NADs
Language: Английский
Citations
53
Chemical Reviews, Journal Year: 2024, Volume and Issue: 124(3), P. 929 - 1033
Published: Jan. 29, 2024
RNA-based therapies have catalyzed a revolutionary transformation in the biomedical landscape, offering unprecedented potential disease prevention and treatment. However, despite their remarkable achievements, these encounter substantial challenges including low stability, susceptibility to degradation by nucleases, prominent negative charge, thereby hindering further development. Chemically modified platforms emerged as strategic innovation, focusing on precise alterations either RNA moieties or associated delivery vectors. This comprehensive review delves into platforms, underscoring significance augmenting performance translational prospects of therapeutics. It encompasses an in-depth analysis various chemically that been instrumental propelling therapeutics toward clinical utility. Moreover, scrutinizes rationale behind diverse chemical modification techniques aiming at optimizing therapeutic efficacy molecules, facilitating robust management. Recent empirical studies corroborating enhancement through modifications are highlighted. Conclusively, we offer profound insights transformative impact drugs delineates prospective trajectories for future development integration.
Language: Английский
Citations
51
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
47
Advanced Materials, Journal Year: 2024, Volume and Issue: 36(15)
Published: Jan. 17, 2024
Abstract Nanotechnology profoundly affects the advancement of medicine. Limitations in diagnosing and treating cancer chronic diseases promote growth nanomedicine. However, there are very few analytical descriptive studies regarding trajectory nanomedicine, key research powers, present landscape, focal investigative points, future outlooks. Herein, articles reviews published Science Citation Index Expanded Web Core Collection from first January 2000 to 18th July 2023 analyzed. a bibliometric visualization publication trends, countries/regions, institutions, journals, categories, themes, references, keywords is produced elaborated. Nanomedicine‐related academic output increasing since COVID‐19 pandemic, solidifying uneven global distribution performance. While China leads terms quantity has numerous highly productive USA advantages impact, commercialization, industrial value. Nanomedicine integrates with other disciplines, establishing interdisciplinary platforms, which drug delivery nanoparticles remain points. Current focuses on integrating nanomedicine cell ferroptosis induction immunotherapy. The keyword “burst testing” identifies promising directions, including immunogenic death, chemodynamic therapy, tumor microenvironment, immunotherapy, extracellular vesicles. prospects, major challenges, barriers addressing these directions discussed.
Language: Английский
Citations
39
ACS Nano, Journal Year: 2025, Volume and Issue: unknown
Published: Feb. 6, 2025
Lipid nanoparticles (LNPs) have emerged as a groundbreaking delivery system for vaccines and therapeutic mRNAs. Ionizable lipids are the most pivotal component of LNPs due to their ability electrostatically interact with mRNA, allowing its encapsulation while concurrently enabling endosomal escape following cellular internalization. Thus, extensive research has been performed optimize ionizable lipid structure develop formulations that well tolerated allow efficient targeting different organs result in high sustained mRNA expression. However, one facet lipids' mostly overlooked: linker segment between headgroup tails. Here, we screened rationally designed library biodegradable linkers. We extensively characterized formulated using these elucidated how minor structural changes radically influenced LNPs' biodistribution vivo. showed use amide urea linkers can modulate pKa, resulting an improved specificity lung transfection. Finally, demonstrated (lipid 35) form entrapping bacterial toxin [pseudomonas exotoxin A (mmPE)] reduced tumor burden significantly increased survival mice metastasis.
Language: Английский
Citations
6
Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown
Published: Jan. 1, 2025
Lipid nanoparticles (LNPs) have emerged as pivotal vehicles for messenger RNA (mRNA) delivery to hepatocytes upon systemic administration and antigen-presenting cells following intramuscular injection. However, achieving mRNA non-hepatocytes remains challenging without the incorporation of targeting ligands such antibodies, peptides, or small molecules. Inspired by comb-like polymeric architecture, here we utilized a multiarm-assisted design construct library 270 dendron-like degradable ionizable lipids altering structures amine heads multiarmed tails optimal delivery. Following in vitro high-throughput screening, series top-dendron-like LNPs with high transfection efficacy were identified. These facilitated greater spleen vivo compared lipid analogs lacking structure. Proteomic analysis corona-LNP pellets showed enhancement key protein clusters, suggesting potential endogenous spleen. A lead LNP formulation, 18-2-9b2, was further used encapsulate Cre demonstrated excellent genome modification splenic macrophages, outperforming spleen-tropic MC3/18PA Ai14 mice model. Moreover, 18-2-9b2 encapsulating therapeutic BTB domain CNC homologue 1 (BACH1) exhibited proficient BACH1 expression subsequent Spic downregulation red pulp macrophages (RPM) Spic-GFP transgene model intravenous administration. results underscore facilitatem potentially opening avenues range mRNA-LNP applications, including regenerative medicine, replacement, gene editing therapies.
Language: Английский
Citations
3
Molecular Pharmaceutics, Journal Year: 2025, Volume and Issue: unknown
Published: Jan. 29, 2025
Lipid-mediated delivery of active pharmaceutical ingredients (API) opened new possibilities in advanced therapies. By encapsulating an API into a lipid nanocarrier (LNC), one can safely deliver APIs not soluble water, those with otherwise strong adverse effects, or very fragile ones such as nucleic acids. However, for the rational design LNCs, detailed understanding composition-structure-function relationships is missing. This review presents currently available computational methods LNC investigation, screening, and design. The state-of-the-art physics-based approaches are described, focus on molecular dynamics simulations all-atom coarse-grained resolution. Their strengths weaknesses discussed, highlighting aspects necessary obtaining reliable results simulations. Furthermore, machine learning, i.e., data-based approach to lipid-mediated introduced. data produced by experimental theoretical provide valuable insights. Processing these help optimize LNCs better performance. In final section this Review, computer reviewed, specifically addressing compatibility
Language: Английский
Citations
2