Increasing the siRNA knockdown efficiency of lipid nanoparticles by morphological transformation with the use of dihydrosphingomyelin as a helper lipid

Hashimoto, Masahiro; Yonezawa, Sei; Furan, Song; Nitta, Chiori; Maeda, Noriyuki; Tomita, Koji; Yokouchi, Ayano; Koide, Hiroyuki; Asai, Tomohiro

doi:10.1039/d3bm00068k

Cited by 2 publications

(2 citation statements)

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“…461 Recently developed DOP-DEDA LNPs exhibit modulated siRNA knockdown efficiency and apparent pK a , influenced by their morphological characteristics. 462 Another exemplary helper lipid, 1,2-distearoyl-snglycero-3-phosphocholine (DSPC), has been effectively employed in the formulation of four-component bilayer (4CB) LNPs that include ionizable and PEGylated lipids, alongside cholesterol, thereby enhancing the stability of RNAloaded LNPs. 463 In summary, the appropriate balance among particle stability, prolonged systemic circulation time, and LNP destabilization inside the targeted cells to release RNA therapeutics is crucial in designing LNPs.…”

Section: Chemical Modifications On Rna Nanodelivery Platformsmentioning

confidence: 99%

“…Lipids like DOTAP display lung-tropism, reducing immune cell infiltration in pulmonary tissues compared to neutral or anionic lipid formulations . Recently developed DOP-DEDA LNPs exhibit modulated siRNA knockdown efficiency and apparent p K a , influenced by their morphological characteristics . Another exemplary helper lipid, 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), has been effectively employed in the formulation of four-component bilayer (4CB) LNPs that include ionizable and PEGylated lipids, alongside cholesterol, thereby enhancing the stability of RNA-loaded LNPs …”

Section: Chemical Modifications On Rna Nanodelivery Platformsmentioning

confidence: 99%

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Chemically Modified Platforms for Better RNA Therapeutics

Shi,

Zhen,

Zhang

et al. 2024

Chem. Rev.

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RNA-based therapies have catalyzed a revolutionary transformation in the biomedical landscape, offering unprecedented potential in disease prevention and treatment. However, despite their remarkable achievements, these therapies encounter substantial challenges including low stability, susceptibility to degradation by nucleases, and a prominent negative charge, thereby hindering further development. Chemically modified platforms have emerged as a strategic innovation, focusing on precise alterations either on the RNA moieties or their associated delivery vectors. This comprehensive review delves into these platforms, underscoring their significance in augmenting the performance and translational prospects of RNA-based therapeutics. It encompasses an in-depth analysis of various chemically modified delivery platforms that have been instrumental in propelling RNA therapeutics toward clinical utility. Moreover, the review scrutinizes the rationale behind diverse chemical modification techniques aiming at optimizing the therapeutic efficacy of RNA molecules, thereby facilitating robust disease management. Recent empirical studies corroborating the efficacy enhancement of RNA therapeutics through chemical modifications are highlighted. Conclusively, we offer profound insights into the transformative impact of chemical modifications on RNA drugs and delineates prospective trajectories for their future development and clinical integration. CONTENTS1. Introduction 930 2. Current Status and Challenges of RNA Therapeutics in Clinics 933 2.1. Molecular Mechanisms and Clinical Research Progress of RNAs 934 2.1.1. ASO 934 2.1.2. siRNA 934 2.1.3. Aptamer 936 2.1.4. mRNA 936 2.1.5. RNA Therapeutics on the Cusp of Clinical Breakthroughs 938 2.2. Major Challenges of Current RNA Therapeutics in Clinics 940 2.

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Section: Chemical Modifications On Rna Nanodelivery Platformsmentioning

confidence: 99%

Section: Chemical Modifications On Rna Nanodelivery Platformsmentioning

confidence: 99%

Chemically Modified Platforms for Better RNA Therapeutics

Shi,

Zhen,

Zhang

et al. 2024

Chem. Rev.

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Theranostic Lipid Nanoparticles for Renal Cell Carcinoma

Mao,

Wang,

Wang

et al. 2023

Advanced Materials

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Renal cell carcinoma (RCC) is a common urological malignancy and represents a leading threat to healthcare. Recent years have seen a series of progresses in the early diagnosis and management of RCC. Theranostic lipid nanoparticles (LNPs) are increasingly one of the focuses in this field, because of their suitability for tumor targeting and multimodal therapy. LNPs can be precisely fabricated with desirable chemical compositions and biomedical properties, which closely match the physiological characteristics and clinical needs of RCC. Herein, a comprehensive review of theranostic LNPs is presented, emphasizing the generic tool nature of LNPs in developing advanced micro‐nano biomaterials. It begins with a brief overview of the compositions and formation mechanism of LNPs, followed with an introduction to kidney‐targeting approaches, such as passive, active, and stimulus responsive targeting. With examples provided, a series of modification strategies for enhancing the tumor targeting and functionality of LNPs were discussed. Thereafter, research advances on applications of these LNPs for RCC including bioimaging, liquid biopsy, drug delivery, physical therapy, and gene therapy are summarized and discussed from an interdisciplinary perspective. The final part highlights the milestone achievements of translation medicine, current challenges as well as future development directions of LNPs for the diagnosis and treatment of RCC.This article is protected by copyright. All rights reserved

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Increasing the siRNA knockdown efficiency of lipid nanoparticles by morphological transformation with the use of dihydrosphingomyelin as a helper lipid

Abstract: Lipid nanoparticles (LNPs) containing dioleoylglycerophosphate-diethylenediamine conjugate (DOP-DEDA) (DOP-DEDA LNPs) show marked morphological transformation and significantly different knockdown efficiency of siRNA when different helper lipids are used.

Cited by 2 publications

References 42 publications

Chemically Modified Platforms for Better RNA Therapeutics

Chemically Modified Platforms for Better RNA Therapeutics

Theranostic Lipid Nanoparticles for Renal Cell Carcinoma

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