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
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
187
Advanced Drug Delivery Reviews, Год журнала: 2023, Номер 200, С. 114990 - 114990
Опубликована: Июль 7, 2023
Язык: Английский
Процитировано
95
Nature Reviews Drug Discovery, Год журнала: 2024, Номер 23(9), С. 709 - 722
Опубликована: Июль 4, 2024
Язык: Английский
Процитировано
78
Advanced Materials, Год журнала: 2023, Номер 36(4)
Опубликована: Авг. 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.
Язык: Английский
Процитировано
59
Nature Nanotechnology, Год журнала: 2023, Номер 19(4), С. 428 - 447
Опубликована: Дек. 27, 2023
Язык: Английский
Процитировано
59
Advanced Drug Delivery Reviews, Год журнала: 2023, Номер 200, С. 115042 - 115042
Опубликована: Авг. 2, 2023
The concept of using mRNA to produce its own medicine in situ the body makes it an ideal drug candidate, holding great potential revolutionize way we approach medicine. unique characteristics mRNA, as well customizable biomedical functions, call for rational design delivery systems protect and transport molecules. In this review, a nanoparticle toolkit is presented development mRNA-based therapeutics from perspective. Nano-delivery derived either natural or chemical synthesis, nature organic inorganic materials, are summarised. Delivery strategies controlling tissue targeting release, role nanoparticles building boosting activity drugs, have also been introduced. end, our insights into clinical translational nano-drugs presented.
Язык: Английский
Процитировано
54
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
53
Nature Communications, Год журнала: 2023, Номер 14(1)
Опубликована: Окт. 13, 2023
Abstract Ocular delivery of lipid nanoparticle (LNPs) packaged mRNA can enable efficient gene and editing. We generated LNP variants through the inclusion positively charged-amine-modified polyethylene glycol (PEG)-lipids (LNPa), negatively charged-carboxyl-(LNPz) carboxy-ester (LNPx) modified PEG-lipids, neutral unmodified PEG-lipids (LNP). Subretinal injections LNPa containing Cre in mouse show tdTomato signal retinal pigmented epithelium (RPE) like conventional LNPs. Unexpectedly, LNPx LNPz 27% 16% photoreceptor transfection, respectively, with striking localization extending from synaptic pedicle to outer segments, displaying pan-retinal distribution photoreceptors RPE. Cas9 sgAi9 leads formation an oval elongated structure a charge resulting 16.4% editing restricted Surface modifications LNPs PEG alter cellular tropism mRNA. genome retina future be used correct genetic mutations that lead blindness.
Язык: Английский
Процитировано
49
Proceedings of the National Academy of Sciences, Год журнала: 2024, Номер 121(11)
Опубликована: Март 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
Язык: Английский
Процитировано
36
Advanced Science, Год журнала: 2024, Номер 11(32)
Опубликована: Июнь 21, 2024
Abstract Funduscopic diseases, including diabetic retinopathy (DR) and age‐related macular degeneration (AMD), significantly impact global visual health, leading to impaired vision irreversible blindness. Delivering drugs the posterior segment of eye remains a challenge due presence multiple physiological anatomical barriers. Conventional drug delivery methods often prove ineffective may cause side effects. Nanomaterials, characterized by their small size, large surface area, tunable properties, biocompatibility, enhance permeability, stability, targeting drugs. Ocular nanomaterials encompass wide range, lipid nanomaterials, polymer metal carbon quantum dot so on. These innovative materials, combined with hydrogels exosomes, are engineered address mechanisms, macrophage polarization, reactive oxygen species (ROS) scavenging, anti‐vascular endothelial growth factor (VEGF). Compared conventional modalities, nanomedicines achieve regulated sustained delivery, reduced administration frequency, prolonged action, minimized This study delves into obstacles encountered in highlights progress facilitated nanomedicine. Prospectively, these findings pave way for next‐generation ocular systems deeper clinical research, aiming refine treatments, alleviate burden on patients, ultimately improve health globally.
Язык: Английский
Процитировано
26