Effects of PEG anchors in PEGylated siRNA lipoplexes on in�vitro gene‑silencing effects and siRNA biodistribution in mice

Hattori, Yoshiyuki; Sakasai, Sho; Ozaki, Kei-ichi; Onishi, Hiraku

doi:10.3892/mmr.2020.11525

Cited by 27 publications

(40 citation statements)

References 21 publications

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“…Aliquots (10 µl) of supernatants were mixed with 50 µl of PicaGene MelioraStar-LT Luminescence Reagent (Toyo Ink Mfg. Co. Ltd.), and luminescence was measured as described ( 14 ). The protein concentration in the supernatants was determined using Pierce™ BCA Protein Assay Kits (Thermo Fisher Scientific, Inc.).…”

Section: Methodsmentioning

confidence: 99%

“…Erythrocytes were separated as described ( 14 ) from whole blood (0.3 ml) collected from the jugular vein of an 8-week-old female BALB/c mouse (Sankyo Labo Service Corp., Inc.) under anesthesia induced by isoflurane inhalation (4% for induction and 1.5–2% for maintenance; FUJIFILM Wako Pure Chemical Corporation). Lipoplexes containing siRNA (2 µg) were then incubated with 100 µl of 2% (v/v) erythrocyte suspension for 15 min at 37°C, then samples on glass plates were assessed by phase-contrast microscopy.…”

Section: Methodsmentioning

confidence: 99%

“…Tissues were analyzed by Cy5.5 fluorescence imaging using a NightOWL LB981 NC100 system (Berthold Technologies GmbH & Co. KG., Bad Wildbad, Germany) as described ( 14 ).…”

Section: Methodsmentioning

confidence: 99%

“…Size and ζ-potential of cationic liposomes and siRNA lipoplexes. The particle size distributions and ζ-potentials of cationic liposomes and siRNA lipoplexes were measured using an ELS-Z2 light-scattering photometer (Otsuka Electronics Co., Ltd.) at 25˚C after dispersion in ~1.5 ml of water as described (14).…”

Section: Preparation Of Cationic Liposomes and Sirna Lipoplexesmentioning

confidence: 99%

“…Tissues were analyzed by Cy5.5 fluorescence imaging using a NightOWL LB981 NC100 system (Berthold Technologies GmbH & Co. KG., Bad Wildbad, Germany) as described (14). Tie2 mRNA levels in the lungs after systemically injecting mice with siRNA lipoplexes.…”

Section: Preparation Of Cationic Liposomes and Sirna Lipoplexesmentioning

confidence: 99%

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Effects of sterol derivatives in cationic liposomes on biodistribution and gene-knockdown in the lungs of mice systemically injected with siRNA lipoplexes

et al. 2021

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Cationic liposomes can be intravenously injected to deliver short interfering (si)RNAs into the lungs. The present study investigated the effects of sterol derivatives in systemically injected siRNA/cationic liposome complexes (siRNA lipoplexes) on gene-knockdown in the lungs of mice. Cationic liposomes composed of 1,2-dioleoyl-3-trimethylammonium-propane or dimethyldioctadecylammonium bromide (DDAB) were prepared as a cationic lipid, with sterol derivatives such as cholesterol (Chol), β-sitosterol, ergosterol (Ergo) or stigmasterol as a neutral helper lipid. Transfected liposomal formulations composed of DDAB/Chol or DDAB/Ergo did not suppress the expression of the luciferase gene in LLC-Luc and Colon 26-Luc cells in vitro, whereas other formulations induced moderate gene-silencing. The systemic injection of siRNA lipoplexes formulated with Chol or Ergo into mice resulted in abundant siRNA accumulation in the lungs. In comparison, systemically injected DDAB/Chol or DDAB/Ergo lipoplexes of Tie2 siRNA effectively increased the suppression of the Tie2 mRNA expression in the lungs of mice. These findings indicated that DDAB/Chol and DDAB/Ergo liposomes could function as vectors for siRNA delivery to the lungs.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…Tissues were analyzed by Cy5.5 fluorescence imaging using a NightOWL LB981 NC100 system (Berthold Technologies GmbH & Co. KG., Bad Wildbad, Germany) as described ( 14 ).…”

Section: Methodsmentioning

confidence: 99%

Section: Preparation Of Cationic Liposomes and Sirna Lipoplexesmentioning

confidence: 99%

Section: Preparation Of Cationic Liposomes and Sirna Lipoplexesmentioning

confidence: 99%

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Effects of sterol derivatives in cationic liposomes on biodistribution and gene-knockdown in the lungs of mice systemically injected with siRNA lipoplexes

et al. 2021

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Transferrin Receptor Targeted Polyplexes Completely Comprised of Sequence‐Defined Components

Benli-Hoppe

Öztürk

et al. 2021

Macromol. Rapid Commun.

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Human transferrin protein (Tf ) modified polyplexes have already displayed encouraging potential for receptor-mediated nucleic acid delivery into tumors. The use of a blood-derived targeting protein and polydisperse macromolecular cationic subunits however presents a practical challenge for pharmaceutical grade production. Here, Tf receptor (TfR) targeted small interfering RNA (siRNA) polyplexes are designed that are completely composed of synthetic, monodisperse, and sequence-defined subunits generated by solid-phase supported synthesis. An optimized cationizable lipo-oligoaminoamide (lipo-OAA) is used for siRNA core polyplex formation, and a retro-enantio peptide (reTfR) attached via a monodisperse polyethylene glycol (PEG) spacer via click chemistry is applied for targeting. Improved gene silencing is demonstrated in TfR-expressing KB and DU145 cells. Analogous plasmid DNA (pDNA) polyplexes are successfully used for receptor-mediated gene delivery in TfR-rich K562 cells and Neuro2a cells. Six lipo-OAAs differing in their lipidic domain and redox-sensitive attachment of lipid residues are tested in order to evaluate the impact of core polyplex stability on receptor-dependent gene transfer.

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Oral delivery of RNAi for cancer therapy

Afrin

Bai

Kumar

et al. 2023

Cancer Metastasis Rev

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Cancer is a major health concern worldwide and is still in a continuous surge of seeking for effective treatments. Since the discovery of RNAi and their mechanism of action, it has shown promises in targeted therapy for various diseases including cancer. The ability of RNAi to selectively silence the carcinogenic gene makes them ideal as cancer therapeutics. Oral delivery is the ideal route of administration of drug administration because of its patients’ compliance and convenience. However, orally administered RNAi, for instance, siRNA, must cross various extracellular and intracellular biological barriers before it reaches the site of action. It is very challenging and important to keep the siRNA stable until they reach to the targeted site. Harsh pH, thick mucus layer, and nuclease enzyme prevent siRNA to diffuse through the intestinal wall and thereby induce a therapeutic effect. After entering the cell, siRNA is subjected to lysosomal degradation. Over the years, various approaches have been taken into consideration to overcome these challenges for oral RNAi delivery. Therefore, understanding the challenges and recent development is crucial to offer a novel and advanced approach for oral RNAi delivery. Herein, we have summarized the delivery strategies for oral delivery RNAi and recent advancement towards the preclinical stages.

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Effects of PEG anchors in PEGylated siRNA lipoplexes on in�vitro gene‑silencing effects and siRNA biodistribution in mice

Cited by 27 publications

References 21 publications

Effects of sterol derivatives in cationic liposomes on biodistribution and gene-knockdown in the lungs of mice systemically injected with siRNA lipoplexes

Effects of sterol derivatives in cationic liposomes on biodistribution and gene-knockdown in the lungs of mice systemically injected with siRNA lipoplexes

Transferrin Receptor Targeted Polyplexes Completely Comprised of Sequence‐Defined Components

Oral delivery of RNAi for cancer therapy

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