Nanoscale, Год журнала: 2024, Номер 16(14), С. 6820 - 6836
Опубликована: Янв. 1, 2024
This review highlights the latest advances in lipid nanoparticle mRNA based nanomedicines under preclinical and clinical investigation.
Язык: Английский
Advanced Materials, Год журнала: 2023, Номер 35(51)
Опубликована: Май 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
Язык: Английский
Процитировано
199
Vaccines, Год журнала: 2023, Номер 11(3), С. 658 - 658
Опубликована: Март 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.
Язык: Английский
Процитировано
69
Advanced Materials, Год журнала: 2023, Номер unknown
Опубликована: Окт. 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
Язык: Английский
Процитировано
56
Nature Communications, Год журнала: 2024, Номер 15(1)
Опубликована: Июль 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.
Язык: Английский
Процитировано
56
Advanced Science, Год журнала: 2023, Номер 10(19)
Опубликована: Апрель 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.
Язык: Английский
Процитировано
55
Chemical Reviews, Год журнала: 2024, Номер 124(3), С. 929 - 1033
Опубликована: Янв. 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.
Язык: Английский
Процитировано
55
Proceedings of the National Academy of Sciences, Год журнала: 2023, Номер 120(50)
Опубликована: Дек. 7, 2023
Ionizable lipid nanoparticles (LNPs) pivotal to the success of COVID-19 mRNA (messenger RNA) vaccines hold substantial promise for expanding landscape mRNA-based therapies. Nevertheless, risk delivery off-target tissues highlights necessity LNPs with enhanced tissue selectivity. The intricate nature biological systems and inadequate knowledge structure–activity relationships emphasize significance high-throughput methods produce chemically diverse libraries screening. Here, we introduce a streamlined approach rapid design synthesis combinatorial biodegradable ionizable lipids. This led identification iso-A11B5C1, an uniquely apt muscle-specific delivery. It manifested high transfection efficiencies in muscle tissues, while significantly diminishing off-targeting organs like liver spleen. Moreover, iso-A11B5C1 also exhibited reduced potency lymph nodes antigen-presenting cells, prompting investigation into influence direct immune cell via on vaccine effectiveness. In comparison SM-102, iso-A11B5C1’s limited attenuated its ability elicit humoral immunity, it remained highly effective triggering cellular responses after intramuscular administration, which is further corroborated by strong therapeutic performance as cancer melanoma model. Collectively, our study not only enriches toolkit generating tissue-specific lipids but encourages reassessment prevailing paradigms design. rethinking principles, suggesting that achieving might be sole criterion developing vaccines.
Язык: Английский
Процитировано
49
Advanced Materials, Год журнала: 2024, Номер 36(15)
Опубликована: Янв. 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.
Язык: Английский
Процитировано
40
Journal of Controlled Release, Год журнала: 2024, Номер 375, С. 366 - 388
Опубликована: Сен. 18, 2024
Recent advancements in RNA therapeutics highlight the critical need for precision gene delivery systems that target specific organs and cells. Lipid nanoparticles (LNPs) have emerged as key vectors delivering mRNA siRNA, offering protection against enzymatic degradation, enabling targeted cellular uptake, facilitating cargo release into cytosol. This review discusses development optimization of organ- cell-specific LNPs, focusing on their design, mechanisms action, therapeutic applications. We explore innovations such DNA/RNA barcoding, which facilitates high-throughput screening precise adjustments formulations. address major challenges, including improving endosomal escape, minimizing off-target effects, enhancing efficiencies. Notable clinical trials recent FDA approvals illustrate practical applications future potential LNP-based therapies. Our findings suggest while considerable progress has been made, continued research is essential to resolve existing limitations bridge gap between pre-clinical evaluation safety efficacy therapeutics. highlights dynamic LNP research. It outlines a roadmap RNA-based medicine.
Язык: Английский
Процитировано
19
ACS Nano, Год журнала: 2025, Номер unknown
Опубликована: Фев. 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.
Язык: Английский
Процитировано
6