Effect of hydrophobic scaffold on the cellular uptake and gene transfection activities of DNA-encapsulating liposomal nanoparticles via intracerebroventricular administration

Akita, Hidetaka; Nakatani, Taichi; Kuroki, Kazuhiko; Maenaka, Katsumi; Tange, Kota; Nakai, Yoshihisa; Harashima, Hideyoshi

doi:10.1016/j.ijpharm.2015.05.043

Cited by 25 publications

(21 citation statements)

References 15 publications

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“…44 The higher uptake of the ssPalmE-LNPs can also be explained by its ApoE-dependent uptake via the LDL-receptor family. 45 The expression of the LRPs in macrophages, especially in the CD169-positive ones, is relatively higher than that in DCs. 46 In the case of the vaccination of dead cells that contain OVA as a model antigen, the selective deletion of CD169 + macrophages in LNs resulted in a significant decrease in vaccination activity.…”

Section: ■ Discussionmentioning

confidence: 97%

Vitamin E Scaffolds of pH-Responsive Lipid Nanoparticles as DNA Vaccines in Cancer and Protozoan Infection

et al. 2020

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DNA vaccinations are promising strategies for treating diseases that require cellular immunity (i.e., cancer and protozoan infection). Here, we report on the use of a liposomal nanocarrier (lipid nanoparticles (LNPs)) composed of an SS-cleavable and pH-activated lipidlike material (ssPalm) as an in vivo DNA vaccine. After subcutaneous administration, the LNPs containing an ssPalmE, an ssPalm with vitamin E scaffolds, elicited a higher gene expression activity in comparison with the other LNPs composed of the ssPalms with different hydrophobic scaffolds. Immunization with the ssPalmE-LNPs encapsulating plasmid DNA that encodes ovalbumin (OVA, a model tumor antigen) or profilin (TgPF, a potent antigen of Toxoplasma gondii) induced substantial antitumor or antiprotozoan effects, respectively. Flow cytometry analysis of the cells that had taken up the LNPs in draining lymph nodes (dLNs) showed that the ssPalmE-LNPs were largely taken up by macrophages and a small number of dendritic cells. We found that the transient deletion of CD169+ macrophages, a subpopulation of macrophages that play a key role in cancer immunity, unexpectedly enhanced the activity of the DNA vaccine. These data suggest that the ssPalmE-LNPs are effective DNA vaccine carriers, and a strategy for avoiding their being trapped by CD169+ macrophages will be a promising approach for developing next-generation DNA vaccines.

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Section: ■ Discussionmentioning

confidence: 97%

Vitamin E Scaffolds of pH-Responsive Lipid Nanoparticles as DNA Vaccines in Cancer and Protozoan Infection

et al. 2020

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“…Since the accumulation of lipoplex in a tumor relies on the enhanced permeability and retention (EPR) effect [ 120 , 121 ], the surface of the lipoplex can be modified with a hydrophilic PEG polymer to increase its circulation time after intravenous injection; otherwise, the lipoplex is rapidly captured by the reticuloendothelial system. On the other hand, it was reported that LNPs without a large amount of PEG modification are highly effective for liver targeting [ 28 , 122 , 123 ]. LNPs prepared with ionizable lipids form a protein corona in the bloodstream [ 124 ].…”

Section: Development Of Lnps For Sirna Therapymentioning

confidence: 99%

“…ApoE in the protein corona is recognized by receptors such as LDLR, which are overexpressed by hepatocytes [ 125 ]. Then, the complexes are internalized into hepatocytes via the ApoE-LDLR pathway [ 28 , 122 , 123 ]. Since the formation of the protein corona in the bloodstream is important for the liver targeting of LNPs, only a small amount of PEG modification (~1% as a molar ratio) of the LNP is standard protocol in the case of liver targeting.…”

Section: Development Of Lnps For Sirna Therapymentioning

confidence: 99%

Recent advances in siRNA delivery mediated by lipid-based nanoparticles

Yonezawa

Koide

Asai

2020

Advanced Drug Delivery Reviews

237

157

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Small interfering RNA (siRNA) has been expected to be a unique pharmaceutic for the treatment of broad-spectrum intractable diseases. However, its unfavorable properties such as easy degradation in the blood and negative-charge density are still a formidable barrier for clinical use. For disruption of this barrier, siRNA delivery technology has been significantly advanced in the past two decades. The approval of Patisiran (ONPATTRO™) for the treatment of transthyretin-mediated amyloidosis, the first approved siRNA drug, is a most important milestone. Since lipid-based nanoparticles (LNPs) are used in Patisiran, LNP-based siRNA delivery is now of significant interest for the development of the next siRNA formulation. In this review, we describe the design of LNPs for the improvement of siRNA properties, bioavailability, and pharmacokinetics. Recently, a number of siRNA-encapsulated LNPs were reported for the treatment of intractable diseases such as cancer, viral infection, inflammatory neurological disorder, and genetic diseases. We believe that these contributions address and will promote the development of an effective LNP-based siRNA delivery system and siRNA formulation.

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“…Neutrally charged, 120–150 nm liposomal NPs containing palmitic acid, vitamin A, or vitamin E preferentially transfected astrocytes close to the injection site after ICV delivery. In vitro , apolipoprotein E (ApoE) co-treatment increased uptake and transfection efficiency lipid NP derived from vitamin A and E in astrocyte-derived cells (Akita et al, 2015). …”

Section: Delivery Systemsmentioning

confidence: 99%

“…Since hypoxia-inducible factor-1 binds to hypoxia response element, VEGF expression was enhanced during stroke (Shen et al, 2008). Uptake and transfection efficiency of lipid NP uptake and transfection efficiency increased in the presence of ApoE suggesting that it could be utilized for astrocyte targeting (Akita et al, 2015). …”

Section: Cns-targeted Gene Delivery Using Cell-specific Promotersmentioning

confidence: 99%

Destination Brain: the Past, Present, and Future of Therapeutic Gene Delivery

Joshi

Labhasetwar

Ghorpade

2017

J Neuroimmune Pharmacol

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Neurological diseases and disorders (NDDs) present a significant societal burden and currently available drug- and biological-based therapeutic strategies have proven inadequate to alleviate it. Gene therapy is a suitable alternative to treat NDDs compared to conventional systems since it can be tailored to specifically alter select gene expression, reverse disease phenotype and restore normal function. The scope of gene therapy has broadened over the years with the advent of RNA interference and genome editing technologies. Consequently, encouraging results from central nervous system (CNS)-targeted gene delivery studies have led to their transition from preclinical to clinical trials. As we shift to an exciting gene therapy era, a retrospective of available literature on CNS-associated gene delivery is in order. This review is timely in this regard, since it analyzes key challenges and major findings from the last two decades and evaluates future prospects of brain gene delivery. We emphasize major areas consisting of physiological and pharmacological challenges in gene therapy, function-based selection of an ideal cellular target, available therapy modalities, and diversity of viral vectors and nanoparticles as vehicle systems. Further, we present plausible answers to key questions such as strategies to circumvent low blood-brain barrier permeability, most suitable CNS cell types for targeting. We compare and contrast pros and cons of the tested viral vectors in context of delivery systems used in past and current clinical trials. Gene vector design challenges are also evaluated in the context of cell-specific promoters. Key challenges and findings reported for recent gene therapy clinical trials, assessing viral vectors and nanoparticles, are discussed in the context of bench to bedside gene therapy translation. We conclude this review by tying together gene delivery challenges, available vehicle systems and comprehensive analysis of neuropathogenesis to outline future prospects of CNS-targeted gene therapies.

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Effect of hydrophobic scaffold on the cellular uptake and gene transfection activities of DNA-encapsulating liposomal nanoparticles via intracerebroventricular administration

Cited by 25 publications

References 15 publications

Vitamin E Scaffolds of pH-Responsive Lipid Nanoparticles as DNA Vaccines in Cancer and Protozoan Infection

Vitamin E Scaffolds of pH-Responsive Lipid Nanoparticles as DNA Vaccines in Cancer and Protozoan Infection

Recent advances in siRNA delivery mediated by lipid-based nanoparticles

Destination Brain: the Past, Present, and Future of Therapeutic Gene Delivery

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