PD-1 siRNA-Encapsulated Solid Lipid Nanoparticles Downregulate PD-1 Expression by Macrophages and Inhibit Tumor Growth

Hanafy, Mahmoud S.; Hufnagel, Stephanie; Trementozzi, Andrea N.; Sakran, Wedad; Stachowiak, Jeanne C.; Koleng, John J.; Cui, Zhengrong

doi:10.1208/s12249-021-01933-y

Cited by 11 publications

(9 citation statements)

References 35 publications

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“…Intratumoral injection [206] Stable nucleic acid-lipid nanoparticle Enable high encapsulation Efficiency of nucleic acids with improved cellular uptake and subsequent release…”

Section: Pd-1 Melanomamentioning

confidence: 99%

Emerging Progress of RNA-Based Antitumor Therapeutics

Fu¹,

Dong²,

Wu³

et al. 2023

Int. J. Biol. Sci.

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RNA-based therapeutics (e.g., mRNAs, siRNAs, microRNAs, ASOs, and saRNAs) have considerable potential for tumor treatment. The development and optimization of RNA modifications and delivery systems enable the stable and efficient delivery of RNA cargos in vivo to elicit an antitumor response. Targeted RNA-based therapeutics with multiple specificities and high efficacies are now available. In this review, we discuss progress in RNA-based antitumor therapeutics, including mRNAs, siRNAs, miRNAs, ASOs, saRNAs, RNA aptamers, and CRISPR-based gene editing. We focus on the immunogenicity, stability, translation efficiency, and delivery of RNA drugs, and summarize their optimization and the development of delivery systems. In addition, we describe the mechanisms by which RNA-based therapeutics induce antitumor responses. Furthermore, we review the merits and limitations of RNA cargos and their therapeutic potential for cancers.

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“…Intratumoral injection [206] Stable nucleic acid-lipid nanoparticle Enable high encapsulation Efficiency of nucleic acids with improved cellular uptake and subsequent release…”

Section: Pd-1 Melanomamentioning

confidence: 99%

Emerging Progress of RNA-Based Antitumor Therapeutics

Fu¹,

Dong²,

Wu³

et al. 2023

Int. J. Biol. Sci.

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“…Therefore, LNPs have been recognized as the most effective siRNA delivery system. Ionizable LNPs RBPMS siRNA HEK293-GFP stable cells (GFP293) [157] Ionizable LNPs (CL4H6) STAT3 HIF-1α ICR (♀, 4-10 weeks) mice and BALB/cAjcl-nu/nu (♂, 4-5 weeks) mice [158] Ultra-small LNPs MK siRNA Human HCC cell line, HepG2, and male BALB/c nude mice [159] Ginger-derived NPs (GDNPs) Dmt1 siRNA Hamp KO mice [160] SLNs PD-1 J774A.1 murine macrophages and B16-F10 murine melanoma cells [161] SLNs TNF-α J774A.1 murine macrophages [162]…”

Section: Lipid Nps (Lnps) In Sirna Therapeuticsmentioning

confidence: 99%

Nanoparticle Delivery Platforms for RNAi Therapeutics Targeting COVID-19 Disease in the Respiratory Tract

Zhang

Almazi

Ong

et al. 2022

IJMS

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Since December 2019, a pandemic of COVID-19 disease, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly spread across the globe. At present, the Food and Drug Administration (FDA) has issued emergency approval for the use of some antiviral drugs. However, these drugs still have limitations in the specific treatment of COVID-19, and as such, new treatment strategies urgently need to be developed. RNA-interference-based gene therapy provides a tractable target for antiviral treatment. Ensuring cell-specific targeted delivery is important to the success of gene therapy. The use of nanoparticles (NPs) as carriers for the delivery of small interfering RNA (siRNAs) to specific tissues or organs of the human body could play a crucial role in the specific therapy of severe respiratory infections, such as COVID-19. In this review, we describe a variety of novel nanocarriers, such as lipid NPs, star polymer NPs, and glycogen NPs, and summarize the pre-clinical/clinical progress of these nanoparticle platforms in siRNA delivery. We also discuss the application of various NP-capsulated siRNA as therapeutics for SARS-CoV-2 infection, the challenges with targeting these therapeutics to local delivery in the lung, and various inhalation devices used for therapeutic administration. We also discuss currently available animal models that are used for preclinical assessment of RNA-interference-based gene therapy. Advances in this field have the potential for antiviral treatments of COVID-19 disease and could be adapted to treat a range of respiratory diseases.

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“…However, SLNs have the disadvantages of low drug loading and instability. Hanafy et al [108] recently encapsulated PD-1 siRNA in SLN and discovered the encapsulation rate reached 98.9% following physical characterization. In vitro and in vivo research demonstrated that siRNA targeting PD-1 can greatly decrease tumor growth.…”

Section: Solid Lipid Nanoparticlesmentioning

confidence: 99%

Inhaled siRNA Formulations for Respiratory Diseases: From Basic Research to Clinical Application

Fan

Yang

2022

Pharmaceutics

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The development of siRNA technology has provided new opportunities for gene-specific inhibition and knockdown, as well as new ideas for the treatment of disease. Four siRNA drugs have already been approved for marketing. However, the instability of siRNA in vivo makes systemic delivery ineffective. Inhaled siRNA formulations can deliver drugs directly to the lung, showing great potential for treating respiratory diseases. The clinical applications of inhaled siRNA formulations still face challenges because effective delivery of siRNA to the lung requires overcoming the pulmonary and cellular barriers. This paper reviews the research progress for siRNA inhalation formulations for the treatment of various respiratory diseases and summarizes the chemical structural modifications and the various delivery systems for siRNA. Finally, we conclude the latest clinical application research for inhaled siRNA formulations and discuss the potential difficulty in efficient clinical application.

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PD-1 siRNA-Encapsulated Solid Lipid Nanoparticles Downregulate PD-1 Expression by Macrophages and Inhibit Tumor Growth

Cited by 11 publications

References 35 publications

Emerging Progress of RNA-Based Antitumor Therapeutics

Emerging Progress of RNA-Based Antitumor Therapeutics

Nanoparticle Delivery Platforms for RNAi Therapeutics Targeting COVID-19 Disease in the Respiratory Tract

Inhaled siRNA Formulations for Respiratory Diseases: From Basic Research to Clinical Application

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