Drug Delivery of siRNA Therapeutics

Lamberti, Gaetano; Barba, Anna Angela

doi:10.3390/pharmaceutics12020178

Cited by 10 publications

(11 citation statements)

References 13 publications

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“…Small interfering RNA (siRNA) presents remarkable ability due to its silence function to downregulate the expression of disease-relevant genes [ 46 ]. However, siRNAs are large macromolecules negatively charged, which results in the difficulty to cross cell membranes.…”

Section: Discussionmentioning

confidence: 99%

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Long Noncoding RNA Hotair Promotes the Progression and Immune Escape in Laryngeal Squamous Cell Carcinoma through MicroRNA-30a/GRP78/PD-L1 Axis

Yuan

Shen

2022

Journal of Immunology Research

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Homeobox (HOX) transcript antisense RNA (Hotair) is elevated in many cancers significantly. However, the oncogenic role of Hotair in human laryngeal squamous cell carcinoma (LSCC) is still unknown. Thus, we explored the expression profile of Hotair and its function in LSCC. We observed high expression levels of Hotair in six LSCC cell lines compared to the human nasopharyngeal epithelial cell line. Knockdown of Hotair inhibited proliferation and enhanced apoptosis of Tu212 and Hep-2 cell lines in vitro. Moreover, the overexpression of hsa-miR-30a-5p inhibited the expression of GRP78 and PD-L1, but Hotair overexpression in LSCC cells rescues both proteins. Furthermore, the impacts of hsa-miR-30a-5p upregulation on the apoptosis and proliferation of LSCC cells were rescued by overexpression of Hotair. Finally, we combined si-Hotair and a VEGF inhibitor to treat LSCC cells in vitro or in vivo and surprisingly observed a significant inhibition of LSCC growth. In summary, these results indicate that Hotair displays an oncogenic role in both malignancy and immune escape in LSCC related to hsa-miR-30a-5p/GRP78/PD-L1 signaling. Therefore, Hotair may be a potential target for treating LSCC.

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Section: Discussionmentioning

confidence: 99%

“…However, siRNAs are large macromolecules negatively charged, which results in the difficulty to cross cell membranes. On the other hand, they are also easily depredated by plasma enzymes or hepatic/renal clearance sequestration [ 46 ]. These problems severely limit siRNAs' utility in therapy.…”

Section: Discussionmentioning

confidence: 99%

Long Noncoding RNA Hotair Promotes the Progression and Immune Escape in Laryngeal Squamous Cell Carcinoma through MicroRNA-30a/GRP78/PD-L1 Axis

Yuan

Shen

2022

Journal of Immunology Research

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“…Nanoparticles are mere carriers or vehicles to convey and protect the genetic information as they travel to the target cells (6). Several other medications use nanoparticles technology right now and their use will increase more because of their effectiveness in delivery medications to targeted sites without collateral damages to unrelated sites or organs (7)(8)(9).…”

Section: Religious Theoriesmentioning

confidence: 99%

A review of COVID-19 vaccines strategies and anti-vaxxers theories

Adesokan¹,

Obeid²

2021

Af J Clin Exp Micro

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In what is a global record time of getting the COVID-19 vaccines available within 11 months, the world has equally been faced with several myths and conspiracy theories dissuading the public from accepting vaccination as an important measure in the response to the pandemic. We reviewed the leading conspiracy theories and balanced these with the scientific basis of viral transmission and replication and the broad role of vaccination in tackling this challenge. We briefly examined the design of the leading vaccines, and provided recommendations for worldwide COVID-19 distribution, acceptance and use. Keywords: COVID-19, vaccine, anti-vaxxer, review French Title: Un examen des stratégies de vaccins COVID-19 et des théories anti-vaxxers Dans ce qui est un temps record mondial pour obtenir les vaccins COVID-19 disponibles en 11 mois, le monde a également été confronté à plusieurs mythes et théories du complot dissuadant le public d'accepter la vaccination comme une mesure importante dans la réponse à la pandémie. Nous avons passé en revue les principales théories du complot et les avons équilibrées avec la base scientifique de la transmission et de la réplication virales et le rôle général de la vaccination dans la lutte contre ce défi. Nous avons brièvement examiné la conception des principaux vaccins et formulé des recommandations pour la distribution, l'acceptation et l'utilisation du COVID19 dans le monde. Mots clés: COVID-19, vaccin, anti-vaxxer, revue

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“…Small interfering RNA (siRNA)—short double-stranded RNA of 21–23 nucleotides—has proved efficient in potent and highly specific gene silencing, and now several RNAi therapeutics have been approved for the market. 1 , 2 , 3 However, the desirable therapeutic efficacy of siRNA depends on the effective delivery carriers because siRNA plays a therapeutic role only in the cytoplasm and can barely pass through the cell membrane by itself. 1 , 2 , 3 , 4 …”

Section: Introductionmentioning

confidence: 99%

“… 1 , 2 , 3 However, the desirable therapeutic efficacy of siRNA depends on the effective delivery carriers because siRNA plays a therapeutic role only in the cytoplasm and can barely pass through the cell membrane by itself. 1 , 2 , 3 , 4 …”

Section: Introductionmentioning

confidence: 99%

Macrophage membrane- and cRGD-functionalized thermosensitive liposomes combined with CPP to realize precise siRNA delivery into tumor cells

Nai

Zhang

et al. 2022

Molecular Therapy - Nucleic Acids

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Despite the success of small interfering RNAs (siRNAs) in clinical settings, their fast clearance and poor delivery efficiency to target cells still hinder their therapeutic effect. Herein, a new treatment system was constructed by combining thermosensitive liposomes with the macrophage membrane, tumor-targeting cyclic Arg-Gly-Asp peptide, a cell-penetrating peptide, and thermotherapy. The constructed system was found to be thermosensitive and stable; the proteins were inherited from the macrophage membrane. This new system combined with thermotherapy displayed the least uptake by macrophages, the greatest uptake by HepG2 cells, the most obvious HepG2 cell apoptosis, and the strongest inhibition of Bcl-2 mRNA and Bcl-2 protein in HepG2 cells. Moreover, 24 h after system administration in tumor-bearing mice, the most prominent distribution of siRNA was observed in tumors, while almost no siRNA was found in other organs. The strongest inhibition of Bcl-2 mRNA, Bcl-2 protein, and tumors was found in mice that had received the proposed system. In summary, when using the constructed system both in vitro and in mice, less uptake by the reticuloendothelial system, greater accumulation in tumor cells, and improved therapeutic efficacy were observed. Therefore, this new system can deliver siRNA selectively and efficiently, and it is a promising therapeutic candidate for precise tumor-targeted therapy.

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Drug Delivery of siRNA Therapeutics

Abstract: Small interfering RNA (siRNA) is a class of nucleic acid-based drugs (NABDs) able to block gene expression by interaction with mRNA before its translation [...]

Cited by 10 publications

References 13 publications

Long Noncoding RNA Hotair Promotes the Progression and Immune Escape in Laryngeal Squamous Cell Carcinoma through MicroRNA-30a/GRP78/PD-L1 Axis

Long Noncoding RNA Hotair Promotes the Progression and Immune Escape in Laryngeal Squamous Cell Carcinoma through MicroRNA-30a/GRP78/PD-L1 Axis

A review of COVID-19 vaccines strategies and anti-vaxxers theories

Macrophage membrane- and cRGD-functionalized thermosensitive liposomes combined with CPP to realize precise siRNA delivery into tumor cells

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