Targeted delivery of lipid nanoparticle to lymphatic endothelial cells via anti-podoplanin antibody

Sakurai, Yasuhisa; Abe, Nodoka; Yoshikawa, Keito; Oyama, Ryotaro; Ogasawara, Satoshi; Murata, Takeshi; Nakai, Yoshihisa; Tange, Kota; Tanaka, Hiroki; Akita, Hidetaka

doi:10.1016/j.jconrel.2022.06.052

Cited by 16 publications

(9 citation statements)

References 64 publications

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“…3D ). To illustrate, a recent study has shown that azidated anti-podoplanin antibodies could be efficiently coupled to the DBCO-PEG-DSPE-bearing LNPs to achieve lymphatic endothelial cell targeting (Sakurai et al 2022 ). For those targeting moieties that contain carboxylic or amine groups, the classic NHS ester-amine conjugation strategy can be applied for the surface modification of LNPs ( Fig.…”

Section: Surface Engineering Strategiesmentioning

confidence: 99%

“…In another case of spherical nucleic acid (SNA)-modified LNPs, the presence of bands at higher molecular weight than naked T21 DNA was observed in an agarose gel, which confirmed the surface DNA conjugation (Sinegra et al 2021 ). Regarding antibody-modified LNPs, sodium dodecyl sulfate (SDS)-PAGE was commonly employed to validate the conjugation (Katakowski et al 2016 ; Sakurai et al 2022 ). SDS is an anionic surfactant that can disrupt the non-covalent bonds in proteins, allowing for proteins to be separated by their size (or molar mass) in a PAGE gel (Otzen 2011 ).…”

Section: Purification and Characterization Techniquesmentioning

confidence: 99%

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Surface engineering of lipid nanoparticles: targeted nucleic acid delivery and beyond

Lin,

Cheng,

Wei

2023

swwlxb

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Harnessing surface engineering strategies to functionalize nucleic acid-lipid nanoparticles (LNPs) for improved performance has been a hot research topic since the approval of the first siRNA drug, patisiran, and two mRNA-based COVID-19 vaccines, BNT162b2 and mRNA-1273. Currently, efforts have been mainly made to construct targeted LNPs for organ- or cell-type-specific delivery of nucleic acid drugs by conjugation with various types of ligands. In this review, we describe the surface engineering strategies for nucleic acid-LNPs, considering ligand types, conjugation chemistries, and incorporation methods. We then outline the general purification and characterization techniques that are frequently used following the engineering step and emphasize the specific techniques for certain types of ligands. Next, we comprehensively summarize the currently accessible organs and cell types, as well as the other applications of the engineered LNPs. Finally, we provide considerations for formulating targeted LNPs and discuss the challenges of successfully translating the “proof of concept” from the laboratory into the clinic. We believe that addressing these challenges could accelerate the development of surface-engineered LNPs for targeted nucleic acid delivery and beyond.

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Section: Surface Engineering Strategiesmentioning

confidence: 99%

Section: Purification and Characterization Techniquesmentioning

confidence: 99%

Surface engineering of lipid nanoparticles: targeted nucleic acid delivery and beyond

Lin,

Cheng,

Wei

2023

swwlxb

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“…With the development of nanotechnology, LNPs have been developed as a preferred non-viral delivery system for nucleic acids to protect cargo from degradation and mediate their intracellular delivery. [7,8] Typically, LNPs are multicomponent lipid-based systems consisting of a cationic or ionizable lipid and one or more helper lipids (e.g., DOPE, DSPC, cholesterol, etc.). It is reported that DOTAP may play a role in targeted cell delivery as it induces internal charge changes in LNPs and is one of the most widely used cationic lipids.…”

Section: Introductionmentioning

confidence: 99%

Exploration of mRNA nanoparticles based on DOTAP through optimization of the helper lipids

Ma,

Wu,

Peng

et al. 2023

Biotechnology Journal

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Lipid nanoparticles (LNPs) are one of the most efficient carriers for RNA packaging and delivery, and vaccines based on mRNA‐LNPs have received substantial attention since the outbreak of the COVID‐19 pandemic. LNPs based on 1,2‐dioleoyl‐3‐trimethylammonium propane (DOTAP) have been widely used in preclinical and clinical settings. We have previously developed a novel non‐viral gene delivery system called LNP3, which was composed of DOTAP, 1,2‐dioleoyl‐sn‐glycero‐3‐phosphoethanolamine (DOPE), and cholesterol. One of the helper lipids in this carrier was DOPE, which belongs to phospholipids. Given that substituting DOPE with non‐phospholipids as helper lipids can increase the delivery efficiency of some LNPs, this study aimed to examine whether non‐phospholipids can be formulated with DOTAP as helper lipids. We found that monoglycerides with C14:0, C16:0, C18:0, C18:1, and C18:2 mediated mRNA transfection, and the transfection efficiency varied between C18:0, C18:1, and C18:2. Furthermore, substituting of the glycerol with other moieties such as the cholesterol or the ethanolamine similarly mediated mRNA transfection. The introduction of cholesterol can further improve the transfection capacity of some DOTAP‐based LNPs. One of the best‐performing formulations, LNP3‐MO, was used to mediate luciferase‐mRNA expression in vivo, and the luminescence signal was found to be mainly enriched in the lung and spleen. In addition, the level of SARS‐CoV‐2 spike antibody in the serum increased after three doses of LNP3‐MO mediated SARS‐CoV‐2 spike mRNA. Altogether, this study demonstrates that non‐phospholipids are promising helper lipids that can be formulated with DOTAP to facilitate efficient delivery of mRNAs in vitro and in vivo with organ‐specific targeting.This article is protected by copyright. All rights reserved

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“…However, the emerging use of nanoparticle technology in cancer therapy has shown promise in improving the efficacy of anti-angiogenic and chemotherapeutic drug treatments by enhancing their pharmacokinetic properties (9). Moreover, the ability to modify these nanoparticles allows for targeted delivery which can be employed to alleviate anti-cancer immunosuppression such as via endothelial cell regulation (10). This review will therefore summarise the mechanisms leading to the immunosuppressive tumour microenvironment (TME) resulting from the generation of the tumour vasculature's features.…”

Section: Introductionmentioning

confidence: 99%

The mechanistic immunosuppressive role of the tumour vasculature and potential nanoparticle-mediated therapeutic strategies

et al. 2022

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The tumour vasculature is well-established to display irregular structure and hierarchy that is conducive to promoting tumour growth and metastasis while maintaining immunosuppression. As tumours grow, their metabolic rate increases while their distance from blood vessels furthers, generating a hypoxic and acidic tumour microenvironment. Consequently, cancer cells upregulate the expression of pro-angiogenic factors which propagate aberrant blood vessel formation. This generates atypical vascular features that reduce chemotherapy, radiotherapy, and immunotherapy efficacy. Therefore, the development of therapies aiming to restore the vasculature to a functional state remains a necessary research target. Many anti-angiogenic therapies aim to target this such as bevacizumab or sunitinib but have shown variable efficacy in solid tumours due to intrinsic or acquired resistance. Therefore, novel therapeutic strategies such as combination therapies and nanotechnology-mediated therapies may provide alternatives to overcoming the barriers generated by the tumour vasculature. This review summarises the mechanisms that induce abnormal tumour angiogenesis and how the vasculature’s features elicit immunosuppression. Furthermore, the review explores examples of treatment regiments that target the tumour vasculature.

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Targeted delivery of lipid nanoparticle to lymphatic endothelial cells via anti-podoplanin antibody

Cited by 16 publications

References 64 publications

Surface engineering of lipid nanoparticles: targeted nucleic acid delivery and beyond

Surface engineering of lipid nanoparticles: targeted nucleic acid delivery and beyond

Exploration of mRNA nanoparticles based on DOTAP through optimization of the helper lipids

The mechanistic immunosuppressive role of the tumour vasculature and potential nanoparticle-mediated therapeutic strategies

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