Lipid-mRNA nanoparticles landscape for cancer therapy

Li, Yin; Fang, Hengtong; Zhang, Tao; Wang, Yu; Qi, Tingting; Li, Bai; Jiao, Huping

doi:10.3389/fbioe.2022.1053197

Cited by 13 publications

(11 citation statements)

References 78 publications

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“…Furthermore, modification of the nucleotides in IVT‐mRNA to 2‐thiouridine, pseudouridine, and 5‐methyl cytidine led to suppressed immune activation levels. [ 264 ]…”

Section: Biomedical Applications Of Rna‐loaded Lnpmentioning

confidence: 99%

“…[129] While targeted drugs (e.g., EGFR tyrosine kinase inhibitor, JAK2 inhibitor, proteasome inhibitor, or CD20 monoclonal antibody), immune anticancer drugs (e.g., immune checkpoint inhibitors), as well as personalized anticancer drugs have been extensively investigated to treat cancer, the overall survival rate and therapeutic effects of the conventional approaches remain to be improved. [129,[264][265][266][267] As detailed discussion on novel anti-cancer drugs/agents are beyond the scope of this review and have been comprehensively reviewed elsewhere, [268][269][270] and we will instead focus on the latest research on microfluidically synthesized RNAloaded LNP for cancer therapy.…”

Section: Anti-cancer Therapymentioning

confidence: 99%

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High‐Precision Synthesis of RNA‐Loaded Lipid Nanoparticles for Biomedical Applications

Seo

Jeon

Kwon

et al. 2023

Adv Healthcare Materials

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The recent development of RNA-based therapeutics in delivering nucleic acids for gene editing and regulating protein translation has led to the effective treatment of various diseases including cancer, inflammatory and genetic disorder, as well as infectious diseases. Among these, lipid nanoparticles (LNP) have emerged as a promising platform for RNA delivery and have shed light by resolving the inherent instability issues of naked RNA and thereby enhancing the therapeutic potency. These LNP consisting of ionizable lipid, helper lipid, cholesterol, and poly(ethylene glycol)-anchored lipid can stably enclose RNA and help them release into the cells' cytosol. Herein, the significant progress made in LNP research starting from the LNP constituents, formulation, and their diverse applications is summarized first. Moreover, the microfluidic methodologies which allow precise assembly of these newly developed constituents to achieve LNP with controllable composition and size, high encapsulation efficiency as well as scalable production are highlighted. Furthermore, a short discussion on current challenges as well as an outlook will be given on emerging approaches to resolving these issues.

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“…Furthermore, modification of the nucleotides in IVT‐mRNA to 2‐thiouridine, pseudouridine, and 5‐methyl cytidine led to suppressed immune activation levels. [ 264 ]…”

Section: Biomedical Applications Of Rna‐loaded Lnpmentioning

confidence: 99%

Section: Anti-cancer Therapymentioning

confidence: 99%

High‐Precision Synthesis of RNA‐Loaded Lipid Nanoparticles for Biomedical Applications

Seo

Jeon

Kwon

et al. 2023

Adv Healthcare Materials

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“…Therefore, it is essential to develop the tumor‐specific delivery systems. By specifically targeting the receptors overexpressed on tumor cell surfaces (e.g., transferrin receptor, folate receptor, and epidermal growth factor receptor), tumor‐specific delivery systems allow novel therapeutic strategies to target immune‐related ncRNAs derived from cancer cells, thereby enhancing the efficacy of ncRNA‐based immunotherapy and reducing the potential of therapeutic resistance (J. Li et al, 2023). Nevertheless, large follow‐up studies and clinical validation are still needed to explore this far‐ranging field (Di Martino et al, 2021; L. Liu et al, 2020).…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Cancer‐derived non‐coding RNAs endow tumor microenvironment with immunosuppressive properties

Hu,

Shi,

et al. 2023

WIREs RNA

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Non‐coding RNAs (ncRNAs) have attracted extensive attention due to their vital roles in tumorigenesis and progression, especially in the immunotherapy resistance. Tumor immunotherapy resistance is a crucial factor hindering the efficacy of tumor treatments, which can be largely attributed to the immunosuppressive properties of tumor microenvironment. Current studies have revealed that cancer‐derived ncRNAs are involved in the formation of tumor immunosuppressive microenvironment (TIME) through multiple ways. They not only promote the expression of immune checkpoint ligands (e.g., PD‐L1, CD47, Gal‐9, and CD276) on cancer cell surfaces, but also enhance the secretion of immunosuppressive cytokines (e.g., TGF‐β, IL‐6, IL‐10, VEGF, and chemokines). Cancer‐derived ncRNAs could also be transferred into surrounding immune‐related cells through extracellular vesicles, thereby inhibiting the cytotoxicity of CD8+T cells and NK cells, restraining the DC‐mediated antigen presentation, inducing the immunosuppressive phenotype transformation of TAMs and CAFs, and enhancing the immunosuppressive functions of Tregs and MDSCs. Herein, we summarize the roles of cancer‐derived ncRNAs in regulating TIME formation and further explore their potential applications as prognostic biomarkers and immunotherapeutic targets, which will help us to address the TIME‐mediated immunotherapy resistance in the future.This article is categorized under: RNA in Disease and Development > RNA in Disease Regulatory RNAs/RNAi/Riboswitches > Regulatory RNAs

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“…For this reason, a detailed understanding of the structure–function relationship of drug-loaded LNP dispersions is of utmost importance. Although considerable efforts have been made in this direction, − research on mRNA-loaded LNP delivery systems using ionizable cationic lipids (mRNA-LNPS) was introduced only recently and the knowledge on the mesoscopic structure and the associated storage stability of the LNP dispersions is still very limited. , Now, the development of ionizable lipids optimized for mRNA-LNPS is very rapid and hundreds of publications and patents are available (cf., e.g., refs − ).…”

Section: Introductionmentioning

confidence: 99%

Mesoscopic Structure of Lipid Nanoparticle Formulations for mRNA Drug Delivery: Comirnaty and Drug-Free Dispersions

Unruh,

Götz,

Vogel

et al. 2024

ACS Nano

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Lipid nanoparticles (LNPs) produced by antisolvent precipitation (ASP) are used in formulations for mRNA drug delivery. The mesoscopic structure of such complex multicomponent and polydisperse nanoparticulate systems is most relevant for their drug delivery properties, medical efficiency, shelf life, and possible side effects. However, the knowledge on the structural details of such formulations is very limited. Essentially no such information is publicly available for pharmaceutical dispersions approved by numerous medicine agencies for the use in humans and loaded with mRNA encoding a mimic of the spike protein of the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) as, e.g., the Comirnaty formulation (BioNTech/Pfizer). Here, we present a simple preparation method to mimic the Comirnaty drugfree LNPs including a comparison of their structural properties with those of Comirnaty. Strong evidence for the liquid state of the LNPs in both systems is found in contrast to the designation of the LNPs as solid lipid nanoparticles by BioNTech. An exceptionally detailed and reliable structural model for the LNPs i.a. revealing their unexpected narrow size distribution will be presented based on a combined small-angle X-ray scattering and photon correlation spectroscopy (SAXS/PCS) evaluation method. The results from this experimental approach are supported by light microscopy, 1 H NMR spectroscopy, Raman spectroscopy, cryogenic electron microscopy (cryoTEM), and simultaneous SAXS/SANS studies. The presented results do not provide direct insights on particle formation or dispersion stability but should contribute significantly to better understanding the LNP drug delivery process, enhancing their medical benefit, and reducing side effects.

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Lipid-mRNA nanoparticles landscape for cancer therapy

Cited by 13 publications

References 78 publications

High‐Precision Synthesis of RNA‐Loaded Lipid Nanoparticles for Biomedical Applications

High‐Precision Synthesis of RNA‐Loaded Lipid Nanoparticles for Biomedical Applications

Cancer‐derived non‐coding RNAs endow tumor microenvironment with immunosuppressive properties

Mesoscopic Structure of Lipid Nanoparticle Formulations for mRNA Drug Delivery: Comirnaty and Drug-Free Dispersions

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