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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.
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Polymeric carriers enhance targeted drug delivery by increasing efficacy while minimizing off-target effects. These carriers comprise a biodegradable polymeric backbone integrated with functional elements that enable targeting, improve physicochemical properties, and regulate drug release.Targeting MechanismsThe targeting ability of polymeric carriers is mediated by a homing device, which is a molecular recognition component designed to selectively bind to specific tissues or cells. Monoclonal...
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Preparation of Neutrally-charged, pH-responsive Polymeric Nanoparticles for Cytosolic siRNA Delivery
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Versatile Nanodelivery Platform to Maximize siRNA Combination Therapy.

Seung Koo Lee1, Benedict Law1, Ching-Hsuan Tung1

  • 1Molecular Imaging Innovations Institute, Department of Radiology, Weill Cornell Medicine, 413 East 69th Street, Box 290, New York, NY, 10021, USA.

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Summary

This study developed a novel nanomedicine for triple-negative breast cancer, combining siRNA and a peptide to target cancer cells and induce apoptosis. This synergistic approach offers a promising new strategy for cancer therapy.

Keywords:
KLA peptideactive targetingnanoplatformsiRNA therapytriple-negative breast cancer

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Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Oncology

Background:

  • Conventional chemotherapy for triple-negative breast cancer (TNBC) has limitations.
  • Developing novel therapeutic combinations is crucial for improved patient outcomes.
  • Co-delivery of multiple agents, like siRNA and peptides, presents formulation challenges.

Purpose of the Study:

  • To design a multifunctional nanomedicine for synergistic cancer treatment.
  • To co-deliver siRNA targeting a prosurvival gene and an organelle-fusing peptide.
  • To target CD44-expressing TNBC cells for enhanced efficacy.

Main Methods:

  • A nanotemplate was engineered using charge-charge interactions.
  • siRNA targeting the p75 neurotrophin receptor and a mitochondria-targeting peptide were incorporated.
  • A CD44 targeting ligand was added for specific cell uptake.
  • The nanomedicine was tested on CD44-expressing TNBC cells.

Main Results:

  • The nanomedicine was efficiently internalized by TNBC cells.
  • Intracellular release of siRNA led to gene silencing.
  • The peptide induced apoptosis by fusing mitochondrial membranes.
  • A synergistic cytotoxic effect was observed from the three-agent combination.

Conclusions:

  • The developed nanomedicine achieves synergistic effects in TNBC treatment.
  • This platform technology can be adapted for co-delivery of various therapeutic agents.
  • The approach minimizes off-targeting effects for maximized therapeutic benefit.