Simultaneous dendritic cells targeting and effective endosomal escape enhance sialic acid-modified mRNA vaccine efficacy and reduce side effects

Tang, Xueying; Zhang, Jiashuo; Sui, Dezhi; Yang, Qiongfen; Wang, Tianyu; Xu, Zihan; Li, Xiaoya; Gao, Xin; Yan, Xinyang; Liu, Xinrong; Song, Yanzhi; Deng, Yihui

doi:10.1016/j.jconrel.2023.11.008

Cited by 14 publications

(4 citation statements)

References 48 publications

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“…ASNPs were formed using a microfluidic method . DM3, cholesterol, DOPE, and DSPE-PEG2000 were dissolved in anhydrous ethanol at a molar ratio of 50:38.5:10:1.5, to obtain a liposome solution (5 mM, calculated based on DM3).…”

Section: Methodsmentioning

confidence: 99%

Co-Delivery of Astaxanthin and siTGF-β1 via Ionizable Liposome Nanoparticles for Improved Idiopathic Pulmonary Fibrosis Therapy

Cao,

Yu,

Cheng

et al. 2024

ACS Appl. Mater. Interfaces

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Alleviating the injury of type II alveolar epithelial cells (AEC 2s) and inhibiting the activation and differentiation of fibroblasts are significant for improving the therapeutic effect of idiopathic pulmonary fibrosis (IPF). To this aim, ionizable liposome nanoparticles (ASNPs) coloaded with antioxidant drug astaxanthin (AST) and small interfering RNA targeting transforming growth factor β1 (siTGF-β1) were developed for enhanced IPF therapy. ASNPs showed high loading and intracellular delivery efficiency for AST and siTGF-β1. After the injection of ASNPs in an IPF mice model, the loaded AST largely scavenged reactive oxygen species (ROS) in the diseased lung to reduce AEC2 apoptosis, thereby ensuring the integrity of the alveolar epithelium. Meanwhile, siTGF-β1, delivered by ASNPs, significantly silenced the expression of TGF-β1 in fibroblasts, inhibiting the differentiation of fibroblasts into myofibroblasts as well as reducing the excessive deposition of extracellular matrix (ECM). The combined use of the two drugs exhibited an excellent synergistic antifibrotic effect and was conducive to minimizing alveolar epithelial damage. This work provides a codelivery strategy of AST and siTGF-β1, which shows great promise for the treatment of IPF by simultaneously reducing alveolar epithelial damage and inhibiting fibroblast activation.

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Section: Methodsmentioning

confidence: 99%

Co-Delivery of Astaxanthin and siTGF-β1 via Ionizable Liposome Nanoparticles for Improved Idiopathic Pulmonary Fibrosis Therapy

Cao,

Yu,

Cheng

et al. 2024

ACS Appl. Mater. Interfaces

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“…Consequently, the lipopolyplexes loading 1 mΨ-modified mRNA offered effective cancer vaccines with minimal induction of systemic cytokine release. Another group used sialic acid to target sialic acid-binding immunoglobulin-like lectin-1 (Siglec-1) expressed on the surface of dendritic cells as a ligand of iLNP [ 192 ]. Interestingly, the introduction of sialic acid to iLNP drastically increased the endosomal escape efficiency.…”

Section: Deliverymentioning

confidence: 99%

mRNA vaccine designs for optimal adjuvanticity and delivery

Mochida,

Uchida

2024

RNA Biology

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Adjuvanticity and delivery are crucial facets of mRNA vaccine design. In modern mRNA vaccines, adjuvant functions are integrated into mRNA vaccine nanoparticles, allowing the co-delivery of antigen mRNA and adjuvants in a unified, all-in-one formulation. In this formulation, many mRNA vaccines utilize the immunostimulating properties of mRNA and vaccine carrier components, including lipids and polymers, as adjuvants. However, careful design is necessary, as excessive adjuvanticity and activation of improper innate immune signalling can conversely hinder vaccination efficacy and trigger adverse effects. mRNA vaccines also require delivery systems to achieve antigen expression in antigen-presenting cells (APCs) within lymphoid organs. Some vaccines directly target APCs in the lymphoid organs, while others rely on APCs migration to the draining lymph nodes after taking up mRNA vaccines. This review explores the current mechanistic understanding of these processes and the ongoing efforts to improve vaccine safety and efficacy based on this understanding.

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“…Additionally, the incorporation of cleavable PEG-lipids enhances cellular uptake and DCs targeting. SA-modified mRNA vaccines exhibit superior efficacy in DCs targeting, enhanced endosomal/lysosomal escape, improved transfection efficiency in DCs, superior tumour treatment effects, and lower side effects compared to commercially formulated mRNA vaccines [116]. In addition, identifying the exact endosomal compartment of escape is also crucial to improve cellular uptake [117] and it still is a debatable aspect.…”

Section: Cellular Uptake and Endosomal Escapementioning

confidence: 99%

Lipid nanoparticles-based RNA therapies for breast cancer treatment

Serpico,

Zhu,

Maia

et al. 2024

Drug Deliv. and Transl. Res.

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Breast cancer (BC) prevails as a major burden on global healthcare, being the most prevalent form of cancer among women. BC is a complex and heterogeneous disease, and current therapies, such as chemotherapy and radiotherapy, frequently fall short in providing effective solutions. These treatments fail to mitigate the risk of cancer recurrence and cause severe side effects that, in turn, compromise therapeutic responses in patients. Over the last decade, several strategies have been proposed to overcome these limitations. Among them, RNA-based technologies have demonstrated their potential across various clinical applications, notably in cancer therapy. However, RNA therapies are still limited by a series of critical issues like off-target effect and poor stability in circulation. Thus, novel approaches have been investigated to improve the targeting and bioavailability of RNA-based formulations to achieve an appropriate therapeutic outcome. Lipid nanoparticles (LNPs) have been largely proven to be an advantageous carrier for nucleic acids and RNA. This perspective explores the most recent advances on RNA-based technology with an emphasis on LNPs’ utilization as effective nanocarriers in BC therapy and most recent progresses in their clinical applications. Graphical Abstract

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Simultaneous dendritic cells targeting and effective endosomal escape enhance sialic acid-modified mRNA vaccine efficacy and reduce side effects

Cited by 14 publications

References 48 publications

Co-Delivery of Astaxanthin and siTGF-β1 via Ionizable Liposome Nanoparticles for Improved Idiopathic Pulmonary Fibrosis Therapy

Co-Delivery of Astaxanthin and siTGF-β1 via Ionizable Liposome Nanoparticles for Improved Idiopathic Pulmonary Fibrosis Therapy

mRNA vaccine designs for optimal adjuvanticity and delivery

Lipid nanoparticles-based RNA therapies for breast cancer treatment

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