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Related Concept Videos

siRNA - Small Interfering RNAs02:30

siRNA - Small Interfering RNAs

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Small interfering RNAs, or siRNAs, are short regulatory RNA molecules that can silence genes post-transcriptionally, as well as the transcriptional level in some cases. siRNAs are important for protecting cells against viral infections and silencing transposable genetic elements.
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the...
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Engineering Lipid-Polymer Nanoparticles for siRNA Delivery to Cancer Cells.

Arthur Manda1, Abdulelah Alhazza1,2, Hasan Uludağ3,4

  • 1Department of Biomedical and Pharmaceutical Sciences, Chapman University School of Pharmacy, Harry and Diane Rinker Health Science Campus, Irvine, CA 92618, USA.

Pharmaceuticals (Basel, Switzerland)
|June 27, 2025
PubMed
Summary
This summary is machine-generated.

Researchers optimized lipid nanoparticles (LNPs) for RNA interference (RNAi) by incorporating polymers. This enhanced cellular uptake and silencing efficiency, offering a promising strategy for targeted cancer treatment.

Keywords:
cancerlipidsnanoparticlespolymerssmall interfering RNA

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Formulating and Characterizing Lipid Nanoparticles for Gene Delivery using a Microfluidic Mixing Platform
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Area of Science:

  • Biotechnology
  • Nanomedicine
  • Molecular Biology

Background:

  • RNA interference (RNAi) holds significant therapeutic potential but faces delivery challenges in clinical settings.
  • Lipid nanoparticles (LNPs) are successful nucleic acid delivery systems, yet lack targeted delivery to solid tumors.
  • Novel polymer-based lipid nanoparticles (LPNPs) are explored to improve safety and efficiency.

Purpose of the Study:

  • To design and optimize novel polymer-based lipid nanoparticles (LPNPs) for enhanced RNA delivery.
  • To investigate the potential of low-molecular-weight polyethyleneimines (PEIs) as replacements for ionizable lipids in LNPs.
  • To improve cellular uptake, reduce cytotoxicity, and increase gene silencing efficiency for cancer therapeutics.

Main Methods:

  • Lipid nanoparticle (LNP) formulations were optimized using response surface methodology (Design Expert) for cellular uptake, cytotoxicity, and silencing efficiency.
  • Mole fractions of lipid components were varied to optimize siRNA delivery.
  • Cationic polymers were integrated as partial or complete replacements for ionizable lipids in optimized LNP formulations.

Main Results:

  • DOPE and Dlin-MC3-DMA were identified as superior components for enhanced efficiency in breast cancer cells compared to DSPC and ALC-0315.
  • Incorporation of specific polymers significantly enhanced cellular internalization of LPNPs.
  • Optimized LPNP formulations demonstrated improved efficiency in delivering nucleic acids.

Conclusions:

  • The study provides a framework for rational LPNP design for enhanced passive targeting and silencing efficiency.
  • These findings support the potential of LPNPs in cancer treatment and broader RNAi applications.
  • Polymer-modified LNPs offer a promising avenue for safer and more effective nucleic acid-based therapies.