Reaction-Activated Disassembly of the NIR-II Probe Enables Fast Detection and Ratiometric Photoacoustic Imaging of Glutathione In Vivo DOI

Yi×ing Zhao,

Lingyun Li, Qiaozhen Ye

et al.

Analytical Chemistry, Journal Year: 2023, Volume and Issue: 95(37), P. 14043 - 14051

Published: Sept. 7, 2023

Glutathione (GSH), the most abundant nonprotein biothiol, is a significant endogenous molecule that plays key role in redox equilibrium vivo and regarded as critical biomarker of cancer. Currently, various fluorescent probes have been designed synthesized for imaging GSH at cellular level visible range first near-infrared window (NIR-I, 750–900 nm). However, application these bioimaging biosensing has extremely hindered by high biobackground low tissue penetration. Herein, based on self-assembly disassembly J-aggregation, we GSH-activatable probe MC-PSE second (NIR-II) fluorescence ratiometric photoacoustic vivo. The anionic cyanine-based tends to form stable J-aggregates an aqueous solution. Upon reaction with GSH, disassembled, emission peak intensity 940 nm significantly increased about 20 times, PA900/PA980 ratio 4 times within 15 min vitro. Notably, used visualize tumor-bearing mice distinguish normal tumor areas successfully virtue NIR-II FL PA dual-modal imaging. design strategy provides novel method imaging, expected be powerful tool accurate detection cancer diagnosis.

Language: Английский

Lipid Nanoparticle (LNP) Enables mRNA Delivery for Cancer Therapy DOI
Yan Zong, Yi Lin, Tuo Wei

et al.

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
Lipid nanoparticles (LNPs) for in vivo RNA delivery and their breakthrough technology for future applications DOI
Michaela Jeong, Yeji Lee, Jeongeun Park

et al.

Advanced Drug Delivery Reviews, Journal Year: 2023, Volume and Issue: 200, P. 114990 - 114990

Published: July 7, 2023

Language: Английский

Citations

94
Nanotechnology-based mRNA vaccines DOI Open Access
Shuying Chen, Xiangang Huang, Yonger Xue

et al.

Nature Reviews Methods Primers, Journal Year: 2023, Volume and Issue: 3(1)

Published: Aug. 17, 2023

Language: Английский

Citations

73
Research Advances on the Stability of mRNA Vaccines DOI Creative Commons
Feiran Cheng, Yi‐Ping Wang, Yu Bai

et al.

Viruses, Journal Year: 2023, Volume and Issue: 15(3), P. 668 - 668

Published: March 2, 2023

Compared to other vaccines, the inherent properties of messenger RNA (mRNA) vaccines and their interaction with lipid nanoparticles make them considerably unstable throughout life cycles, impacting effectiveness global accessibility. It is imperative improve mRNA vaccine stability investigate factors influencing stability. Since structure, excipients, nanoparticle (LNP) delivery systems, manufacturing processes are primary affecting stability, optimizing structure screening excipients can effectively Moreover, improving could also prepare thermally stable safety efficacy. Here, we review regulatory guidance associated summarize key propose a possible research path

Language: Английский

Citations

69
Iterative Design of Ionizable Lipids for Intramuscular mRNA Delivery DOI
Grayson Tilstra, Julien Couture‐Senécal, Yan Ming Anson Lau

et al.

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(4), P. 2294 - 2304

Published: Jan. 18, 2023

Lipid nanoparticles (LNPs) are the most clinically advanced delivery vehicles for RNA and have enabled development of RNA-based drugs such as mRNA COVID-19 vaccines. Functional by an LNP greatly depends on inclusion ionizable lipid, small changes to these lipid structures can significantly improve delivery. However, structure–function relationships between lipids poorly understood, especially LNPs administered intramuscularly. Here, we show that iterative design a novel series generates key structure–activity enables optimization chemically distinct with efficacy is on-par current state art. We find combination comprising ethanolamine core apparent pKa 6.6 6.9 maximizes intramuscular Furthermore, report nonlinear relationship lipid-to-mRNA mass ratio protein expression, suggesting critical exists may depend structure. Our findings add mechanistic understanding demonstrate hydrogen bonding, ionization behavior, parameters affecting validate insights applying them rational new lipids. Overall, our strategy efficiently potent This hypothesis-driven method reveals lay foundation in future LNP-RNA drugs. foresee this be extended other beyond expression.

Language: Английский

Citations

67
Recent Advances in the Lipid Nanoparticle-Mediated Delivery of mRNA Vaccines DOI Creative Commons
K. Swetha, Niranjan G. Kotla, Lakshmi Tunki

et al.

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
Lipid Nanoparticles Optimized for Targeting and Release of Nucleic Acid DOI

Yaru Jia,

Xiu‐Guang Wang,

Luwei Li

et al.

Advanced Materials, Journal Year: 2023, Volume and Issue: 36(4)

Published: Aug. 7, 2023

Abstract Lipid nanoparticles (LNPs) are currently the most promising clinical nucleic acids drug delivery vehicles. LNPs prevent degradation of cargo during blood circulation. Upon entry into cell, specific components lipid can promote endosomal escape acids. These basic properties as acid carriers. As exhibit hepatic aggregation characteristics, enhancing targeting out liver is a crucial way to improve administrated in vivo. Meanwhile, loaded often considered inadequate, and therefore, much effort devoted intracellular release efficiency Here, different strategies efficiently deliver from concluded their mechanisms investigated. In addition, based on information that trials or have completed trials, issues necessary be approached translation discussed, which it hoped will shed light development LNP drugs.

Language: Английский

Citations

56
Recent advances in nanoparticulate RNA delivery systems DOI Creative Commons
Jacob Witten, Yizong Hu, Róbert Langer

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(11)

Published: March 4, 2024

Nanoparticle-based RNA delivery has shown great progress in recent years with the approval of two mRNA vaccines for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and a liver-targeted siRNA therapy. Here, we discuss preclinical clinical advancement new generations therapies along multiple axes. Improvements cargo design such as circularization data-driven untranslated region optimization can drive better expression. New materials discovery research driven improved to extrahepatic targets lung splenic immune cells, which could lead pulmonary gene therapy cancer vaccines, respectively. Other organs even specific cell types be targeted via conjugation small molecule ligands, antibodies, or peptides nanoparticles. Moreover, response any nanoparticle plays crucial role determining efficacy. Targeting increased immunogenicity without induction reactogenic side effects is while minimization important therapies. developments have addressed each these priorities. Last, range trials targeting diverse organs, types, diseases suggest some key advances that may play next wave

Language: Английский

Citations

36
mRNA-Laden Lipid-Nanoparticle-Enabled in Situ CAR-Macrophage Engineering for the Eradication of Multidrug-Resistant Bacteria in a Sepsis Mouse Model DOI

Chunwei Tang,

Weiqiang Jing, Kun Han

et al.

ACS Nano, Journal Year: 2024, Volume and Issue: 18(3), P. 2261 - 2278

Published: Jan. 11, 2024

Sepsis, which is the most severe clinical manifestation of acute infection and has a mortality rate higher than that cancer, represents significant global public health burden. Persistent methicillin-resistant

Language: Английский

Citations

22
mRNA Vaccines Against SARS‐CoV‐2 Variants Delivered by Lipid Nanoparticles Based on Novel Ionizable Lipids DOI
Kepan Chen, Na Fan, Hai Huang

et al.

Advanced Functional Materials, Journal Year: 2022, Volume and Issue: 32(39)

Published: July 19, 2022

Abstract SARS‐CoV‐2 variants are now still challenging all the approved vaccines, including mRNA vaccines. There is an urgent need to develop new generation vaccines with more powerful efficacy and better safety against variants. In this study, a set of ionizable lipids named 4N4T constructed applied form novel lipid nanoparticles called 4N4T‐LNPs. Leading 4N4T‐LNPs exhibit much higher translation efficiency than SM‐102‐LNPs. To test effectiveness delivery system, DS encoding full‐length S protein variant synthesized loaded in The obtained 4N4T‐DS successfully trigger robust durable humoral immune responses its Delta Omicron. Importantly, have RBD‐specific IgG titers neutralizing antibody SM‐102‐based vaccine. Besides, for first time, types vaccine‐induced antibodies found be influenced by chemical structure lipids. also induce strong Th1‐skewed T cell good safety. This work provides vehicle that effective LNPs shows application

Language: Английский

Citations

68