Charge-reversible lipid derivative: A novel type of pH-responsive lipid for nanoparticle-mediated siRNA delivery

Hirai, Yusuke; Ryoko, Saeki; Furan, Song; Koide, Hiroyuki; Fukata, Naoki; Tomita, Koji; Maeda, Noriyuki; Oku, Naoto; Asai, Tomohiro

doi:10.1016/j.ijpharm.2020.119479

Cited by 29 publications

(31 citation statements)

References 45 publications

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“…Taken together, positively charged LNPs have strong cellular affinity but have limited efficacy [47], while negatively charged LNPs show to be transported to lymph node effectively. To take advantage of this charge aspect, chargereversible LNPs have been designed by Hirai et al to achieve the best of both worlds in gene delivery [48]. These LNPs, composed of dipalmitoylphosphatidylcholine (DPPC), cholesterol, and dioleoylglycerophosphate-diethylenediamine conjugate (DOP-DEDA) are positively charged at pH of 6.0, neutral at pH of 7.4 and negatively charged at pH of 8.0.…”

Section: The Properties Of Lipid-based Nanoparticles Governing Their Efficienciesmentioning

confidence: 99%

Lipid-Based Nanoparticles in the Clinic and Clinical Trials: From Cancer Nanomedicine to COVID-19 Vaccines

et al. 2021

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COVID-19 vaccines have been developed with unprecedented speed which would not have been possible without decades of fundamental research on delivery nanotechnology. Lipid-based nanoparticles have played a pivotal role in the successes of COVID-19 vaccines and many other nanomedicines, such as Doxil® and Onpattro®, and have therefore been considered as the frontrunner in nanoscale drug delivery systems. In this review, we aim to highlight the progress in the development of these lipid nanoparticles for various applications, ranging from cancer nanomedicines to COVID-19 vaccines. The lipid-based nanoparticles discussed in this review are liposomes, niosomes, transfersomes, solid lipid nanoparticles, and nanostructured lipid carriers. We particularly focus on the innovations that have obtained regulatory approval or that are in clinical trials. We also discuss the physicochemical properties required for specific applications, highlight the differences in requirements for the delivery of different cargos, and introduce current challenges that need further development. This review serves as a useful guideline for designing new lipid nanoparticles for both preventative and therapeutic vaccines including immunotherapies.

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Section: The Properties Of Lipid-based Nanoparticles Governing Their Efficienciesmentioning

confidence: 99%

Lipid-Based Nanoparticles in the Clinic and Clinical Trials: From Cancer Nanomedicine to COVID-19 Vaccines

et al. 2021

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“…DOP–DEDA exhibits the favorable properties of reduced nonspecific interactions and pH‐responsive ionization, both of which are important for siRNA uptake. [ 119,120 ] DOP–DEDA can be ionized at all physiological pHs but changes charge with pH: positively charged at pH 6.0, neutral at pH 7.4 and negatively charged at pH 8.0, which can reduce aggregation and increase stability. [ 120 ] DOP–DEDA siRNA LNPs disrupt the membrane of red blood cells only at low pH, demonstrating the pH‐dependent interaction between DOP–DEDA LNPs and biological membranes.…”

Section: Environment‐sensitive Lipids For Efficient Sirna Deliverymentioning

confidence: 99%

“…[ 119,120 ] DOP–DEDA can be ionized at all physiological pHs but changes charge with pH: positively charged at pH 6.0, neutral at pH 7.4 and negatively charged at pH 8.0, which can reduce aggregation and increase stability. [ 120 ] DOP–DEDA siRNA LNPs disrupt the membrane of red blood cells only at low pH, demonstrating the pH‐dependent interaction between DOP–DEDA LNPs and biological membranes. DOP–DEDA LNP encapsulating siRNA against polo‐like kinase 1 (siPLK1) highly suppressed the expression of PLK1 mRNA and its protein in MDA‐MB‐231 cells.…”

Section: Environment‐sensitive Lipids For Efficient Sirna Deliverymentioning

confidence: 99%

“…DOP–DEDA LNP encapsulating siRNA against polo‐like kinase 1 (siPLK1) highly suppressed the expression of PLK1 mRNA and its protein in MDA‐MB‐231 cells. [ 120 ] Modification of the LNPs with apolipoprotein E3 (apoE3) resulted in increased cellular uptake of DOP–DEDA in a dose‐dependent manner. [ 120 ] DOP–DEDA LNP utilizes both the clathrin‐ and caveolae‐mediated endocytic pathways to enter cancerous cells.…”

Section: Environment‐sensitive Lipids For Efficient Sirna Deliverymentioning

confidence: 99%

“…[ 120 ] Modification of the LNPs with apolipoprotein E3 (apoE3) resulted in increased cellular uptake of DOP–DEDA in a dose‐dependent manner. [ 120 ] DOP–DEDA LNP utilizes both the clathrin‐ and caveolae‐mediated endocytic pathways to enter cancerous cells. [ 120 ] These findings indicate that DOP–DEDA, as a charge‐reversible lipid, has better stability than conventional ionizable lipids and can serve as an efficacious siRNA delivery vector.…”

Section: Environment‐sensitive Lipids For Efficient Sirna Deliverymentioning

confidence: 99%

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Environment‐Responsive Lipid/siRNA Nanoparticles for Cancer Therapy

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et al. 2020

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RNA interference (RNAi) is a promising technology to regulate oncogenes for treating cancer. The primary limitation of siRNA for clinical application is the safe and efficacious delivery of therapeutic siRNA into target cells. Lipid‐based delivery systems are developed to protect siRNA during the delivery process and to facilitate intracellular uptake. There is a significant progress in lipid nanoparticle systems that utilize cationic and protonatable amino lipid systems to deliver siRNA to tumors. Among these lipids, environment‐responsive lipids are a class of novel lipid delivery systems that are capable of responding to the environment changes during the delivery process and demonstrate great promise for clinical translation for siRNA therapeutics. Protonatable or ionizable amino lipids and switchable lipids as well as pH‐sensitive multifunctional amino lipids are the presentative environment‐responsive lipids for siRNA delivery. These lipids are able to respond to environmental changes during the delivery process to facilitate efficient cytosolic siRNA delivery. Environment‐responsive lipid/siRNA nanoparticles (ERLNP) are developed with the lipids and are tested for efficient delivery of therapeutic siRNA into the cytoplasm of cancer cells to silence target genes for cancer treatment in preclinical development. This review summarizes the recent developments in environment‐response lipids and nanoparticles for siRNA delivery in cancer therapy.

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

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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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Charge-reversible lipid derivative: A novel type of pH-responsive lipid for nanoparticle-mediated siRNA delivery

Cited by 29 publications

References 45 publications

Lipid-Based Nanoparticles in the Clinic and Clinical Trials: From Cancer Nanomedicine to COVID-19 Vaccines

Lipid-Based Nanoparticles in the Clinic and Clinical Trials: From Cancer Nanomedicine to COVID-19 Vaccines

Environment‐Responsive Lipid/siRNA Nanoparticles for Cancer Therapy

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

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