Lipid Nanoparticle-Based Delivery System─A Competing Place for mRNA Vaccines DOI Creative Commons
Xinyu Zhang, Yuanfang Li, Zehua Zhou

et al.

ACS Omega, Journal Year: 2024, Volume and Issue: 9(6), P. 6219 - 6234

Published: Jan. 30, 2024

mRNA, as one of the foci biomedical research in past decade, has become a candidate vaccine solution for various infectious diseases and tumors regenerative medicine immunotherapy due to its high efficiency, safety, effectiveness. A stable effective delivery system is needed protect mRNAs from nuclease degradation while also enhancing immunogenicity. The success mRNA lipid nanoparticles treating COVID-19, certain extent, marks milestone vaccines promotes further on systems. Here, we explore systems, especially (LNPs), considering current status, prospects, challenges nanoparticles, other

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
Current research trends of nanomedicines DOI Creative Commons
Qiuyue Liu, Jiahui Zou, Zhongjian Chen

et al.

Acta Pharmaceutica Sinica B, Journal Year: 2023, Volume and Issue: 13(11), P. 4391 - 4416

Published: May 20, 2023

Owing to the inherent shortcomings of traditional therapeutic drugs in terms inadequate efficacy and toxicity clinical treatment, nanomedicine designs have received widespread attention with significantly improved reduced non-target side effects. Nanomedicines hold tremendous theranostic potential for treating, monitoring, diagnosing, controlling various diseases are attracting an unfathomable amount input research resources. Against backdrop exponentially growing number publications, it is imperative help audience get a panorama image activities field nanomedicines. Herein, this review elaborates on development trends nanomedicines, emerging nanocarriers, vivo fate safety their extensive applications. Moreover, challenges obstacles hindering translation nanomedicines also discussed. The elaboration aspects may enlighten readers set route future endeavors.

Language: Английский

Citations

86
Exploiting RIG-I-like receptor pathway for cancer immunotherapy DOI Creative Commons
Yangfu Jiang, Hongying Zhang, Jiao Wang

et al.

Journal of Hematology & Oncology, Journal Year: 2023, Volume and Issue: 16(1)

Published: Feb. 8, 2023

RIG-I-like receptors (RLRs) are intracellular pattern recognition that detect viral or bacterial infection and induce host innate immune responses. The RLRs family comprises retinoic acid-inducible gene 1 (RIG-I), melanoma differentiation-associated 5 (MDA5) laboratory of genetics physiology 2 (LGP2) have distinctive features. These not only recognize RNA intermediates from viruses bacteria, but also interact with endogenous such as the mislocalized mitochondrial RNA, aberrantly reactivated repetitive transposable elements in human genome. Evasion RLRs-mediated response may lead to sustained infection, defective immunity carcinogenesis. Therapeutic targeting provoke anti-infection effects, anticancer sensitize "immune-cold" tumors checkpoint blockade. In this review, we summarize current knowledge signaling discuss rationale for therapeutic cancer. We describe how can be activated by synthetic oncolytic viruses, mimicry radio-chemotherapy, agonists systemically delivered vivo. integration agonism interference CAR-T cells provides new dimensions complement cancer immunotherapy. Moreover, update progress recent clinical trials therapy involving activation modulation. Further studies mechanisms underlying will shed light on development therapeutics. Manipulation represents an opportunity clinically relevant therapy. Addressing challenges field help develop future generations

Language: Английский

Citations

74
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
A Combinatorial Library of Lipid Nanoparticles for Cell Type‐Specific mRNA Delivery DOI Creative Commons
Gonna Somu Naidu, Seok‐Beom Yong,

Srinivas Ramishetti

et al.

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
From structural design to delivery: mRNA therapeutics for cancer immunotherapy DOI Creative Commons
Feng Zhou, Lujia Huang,

Shiqin Li

et al.

Exploration, Journal Year: 2023, Volume and Issue: 4(2)

Published: Nov. 17, 2023

Abstract mRNA therapeutics have emerged as powerful tools for cancer immunotherapy in accordance with their superiority expressing all sequence‐known proteins vivo. In particular, a small dosage of delivered mRNA, antigen‐presenting cells (APCs) can synthesize mutant neo‐antigens and multi‐antigens present epitopes to T lymphocytes elicit antitumor effects. addition, receptors like chimeric antigen receptor (CAR), T‐cell (TCR), CD134, immune‐modulating factors including cytokines, interferons, antibodies specific enhance immunological response against tumors. With the maturation vitro transcription (IVT) technology, large‐scale pure encoding be synthesized quickly. However, clinical translation mRNA‐based anticancer strategies is restricted by delivering into target organs or inadequate endosomal escape efficiency mRNA. Recently, there been some advances immunotherapy, which roughly classified modifications structure development delivery systems, especially lipid nanoparticle platforms. this review, latest overcoming limitations immunotherapies recent are summarized. Challenges opportunities applications also discussed.

Language: Английский

Citations

50
High-throughput barcoding of nanoparticles identifies cationic, degradable lipid-like materials for mRNA delivery to the lungs in female preclinical models DOI Creative Commons
Lulu Xue, Alex G. Hamilton, Gan Zhao

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Feb. 29, 2024

Abstract Lipid nanoparticles for delivering mRNA therapeutics hold immense promise the treatment of a wide range lung-associated diseases. However, lack effective methodologies capable identifying pulmonary delivery profile chemically distinct lipid libraries poses significant obstacle to advancement therapeutics. Here we report implementation barcoded high-throughput screening system as means identify lung-targeting efficacy cationic, degradable lipid-like materials. We combinatorially synthesize 180 lipids which are initially screened in vitro. then use barcoding technology quantify how selected 96 deliver DNA barcodes vivo. The top-performing nanoparticle formulation Cas9-based genetic editors exhibits therapeutic potential antiangiogenic cancer therapy within lung tumor model female mice. These data demonstrate that employing tool with tropism holds development next-generation extrahepatic platforms.

Language: Английский

Citations

43
Dual mRNA co-delivery for in situ generation of phagocytosis-enhanced CAR macrophages augments hepatocellular carcinoma immunotherapy DOI
Zhenmei Yang, Ying Liu, Kun Zhao

et al.

Journal of Controlled Release, Journal Year: 2023, Volume and Issue: 360, P. 718 - 733

Published: July 19, 2023

Language: Английский

Citations

42
Nanomedomics DOI

Ganghao Liang,

Wanqing Cao, Dongsheng Tang

et al.

ACS Nano, Journal Year: 2024, Volume and Issue: 18(17), P. 10979 - 11024

Published: April 18, 2024

Nanomaterials have attractive physicochemical properties. A variety of nanomaterials such as inorganic, lipid, polymers, and protein nanoparticles been widely developed for nanomedicine via chemical conjugation or physical encapsulation bioactive molecules. Superior to traditional drugs, nanomedicines offer high biocompatibility, good water solubility, long blood circulation times, tumor-targeting Capitalizing on this, several nanoformulations already clinically approved many others are currently being studied in clinical trials. Despite their undoubtful success, the molecular mechanism action vast majority remains poorly understood. To tackle this limitation, herein, review critically discusses strategy applying multiomics analysis study nanomedicines, named nanomedomics, including advantages, applications, future directions. comprehensive understanding could provide valuable insight therefore foster development translation nanomedicines.

Language: Английский

Citations

31
Multicomponent Synthesis of Imidazole-Based Ionizable Lipids for Highly Efficient and Spleen-Selective Messenger RNA Delivery DOI

Wang Dong,

Zhibin Li,

Tailin Hou

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(22), P. 15085 - 15095

Published: May 22, 2024

The spleen emerges as a pivotal target for mRNA delivery, prompting continual quest specialized and efficient lipid nanoparticles (LNPs) designed to enhance spleen-selective transfection efficiency. Here we report imidazole-containing ionizable lipids (IMILs) that demonstrate pronounced preference delivery into the with exceptional We optimized IMIL structures by constructing screening multidimensional library containing multiple heads, tails, linkers perform structure–activity correlation analysis. Following high-throughput in vivo screening, identified A3B7C2 top-performing spleen-specific via formulated LNPs, achieving remarkable 98% proportion of splenic transfection. Moreover, A3B7C2-based LNPs are particularly potent dendritic cell Comparative analyses revealed achieved notable 2.8-fold 12.9-fold increase compared SM102 DLin-MC3-DMA formulations, respectively. Additionally, our approach yielded an 18.3-fold enhancement expression SORT method without introducing additional anionic lipids. Collectively, these IMILs highlight promising avenues further research delivery. This work offers valuable insights swift discovery rational design candidates tailored transfection, thereby facilitating application therapeutics spleen-related interventions.

Language: Английский

Citations

19