Polymer Chemistry, Год журнала: 2024, Номер 15(24), С. 2437 - 2456
Опубликована: Янв. 1, 2024
This review introduces the basic design principles and recent advances in polymeric mRNA therapeutics, highlighting strategies to realize cancer-selective, organ-targeted, tissue-penetrating delivery.
Язык: Английский
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
Advanced Drug Delivery Reviews, Год журнала: 2024, Номер 211, С. 115359 - 115359
Опубликована: Июнь 12, 2024
Язык: Английский
Процитировано
17
Bioactive Materials, Год журнала: 2024, Номер 38, С. 486 - 498
Опубликована: Май 14, 2024
The rapid development of messenger RNA (mRNA) vaccines formulated with lipid nanoparticles (LNPs) has contributed to control the COVID-19 pandemic. However, mRNA have raised concerns about their potential toxicity and clinical safety, including side effects, such as myocarditis, anaphylaxis, pericarditis. In this study, we investigated trehalose glycolipids-containing LNP (LNP S050L) reduce risks associated ionizable lipids. Trehalose glycolipids can form hydrogen bonds polar biomolecules, allowing formation a stable structure by replacing half efficacy safety S050L were evaluated encapsulating encoding luciferase reporter gene measuring expression organ toxicity, respectively. Furthermore, mice immunized an S050L-formulated vaccine expressing influenza hemagglutinin exhibited significant reduction in heart, spleen, liver, while sustaining immune efficiency, compared conventional LNPs (Con-LNPs). Our findings suggest that S050L, glycolipid-based LNP, could facilitate safe improved safety.
Язык: Английский
Процитировано
16
iScience, Год журнала: 2024, Номер 27(6), С. 109804 - 109804
Опубликована: Апрель 23, 2024
Nucleic acid therapeutics offer tremendous promise for addressing a wide range of common public health conditions. However, the
Язык: Английский
Процитировано
14
Journal of Controlled Release, Год журнала: 2024, Номер 372, С. 113 - 140
Опубликована: Июнь 15, 2024
Язык: Английский
Процитировано
14
ACS Applied Materials & Interfaces, Год журнала: 2024, Номер 16(20), С. 25698 - 25709
Опубликована: Май 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.
Язык: Английский
Процитировано
12
Journal of Nanobiotechnology, Год журнала: 2024, Номер 22(1)
Опубликована: Июнь 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
Язык: Английский
Процитировано
12
Pharmaceutics, Год журнала: 2024, Номер 16(12), С. 1521 - 1521
Опубликована: Ноя. 26, 2024
Lipid nanoparticles (LNPs) have shown promise as a delivery system for nucleic acid-based therapeutics, including DNA, siRNA, and mRNA vaccines. The immune plays critical role in the response to these nanocarriers, with innate cells initiating an early adaptive mediating more specific reaction, sometimes leading potential adverse effects. Recent studies that LNPs is mediated by Toll-like receptors (TLRs) other pattern recognition (PRRs), which recognize lipid components of nanoparticles. This can trigger activation inflammatory pathways production cytokines chemokines, effects such fever, inflammation, pain at injection site. On hand, appears be primarily directed against protein encoded cargo, little evidence ongoing LNP itself. Understanding relationship between development safe effective systems. In fact, targeting essential develop vaccines, well therapies cancer or infections. There lack research literature has systematically studied factors influence interaction further needed better elucidate mechanisms underlying LNPs. this review, we discuss LNPs’ composition, physico-chemical properties, size, shape, surface charge, corona formation affect reactivity system, thus providing guide on new formulations could gain favorable efficacy/safety profile.
Язык: Английский
Процитировано
11
Advanced Functional Materials, Год журнала: 2024, Номер 34(27)
Опубликована: Март 5, 2024
Abstract Chimeric antigen receptor (CAR) monocyte and macrophage therapies are promising solid tumor immunotherapies that can overcome the challenges facing conventional CAR T cell therapy. mRNA lipid nanoparticles (mRNA‐LNPs) offer a viable platform for in situ engineering of monocytes with transient tunable expression to reduce off‐tumor toxicity streamline manufacturing. However, identifying LNPs tropism intracellular delivery potency is difficult using traditional screening techniques. Here, ionizable design high‐throughput vivo utilized identify new class oxidized innate monocytes. A library (oLNPs) unoxidized (uLNPs) synthesized evaluate immune cells. oLNPs demonstrate notable differences morphology, ionization energy, p K , thereby enhancing human macrophages, but not Subsequently, DNA barcodes identifies an oLNP formulation, C14‐O2, In proof‐of‐concept study, C14‐O2 LNP used engineer functional CD19‐CAR robust B aplasia (45%) healthy mice. This work highlights utility as macrophages/monocytes
Язык: Английский
Процитировано
10
ACS Nano, Год журнала: 2024, Номер 18(26), С. 17228 - 17239
Опубликована: Июнь 15, 2024
Nanoplastics (NPs) represent a growing concern for global environmental health, particularly in marine ecosystems where they predominantly accumulate. The impact of NPs on benthic organisms, such as bivalves, raises critical questions regarding ecological integrity and food safety. Traditional methods assessing NP toxicity are often limited by their time-intensive nature ethical considerations. Herein, we explore the toxicological effects bivalve
Язык: Английский
Процитировано
7