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Anionic pH-Sensitive Lipoplexes.

Nathalie Mignet1,2,3,4, Daniel Scherman5,6,7,8

  • 1Chimie ParisTech, PSL Research University, Unité de Technologies Chimiques et Biologiques pour la Santé (UTCBS), F-75005 Paris, France. nathalie.mignet@parisdescartes.fr.

Methods in Molecular Biology (Clifton, N.J.)
|November 13, 2016
PubMed
Summary

Researchers developed pH-sensitive, anionic pegylated lipoplexes for gene delivery to tumors. These nanoparticles demonstrate effective DNA delivery and pH-responsive properties in vitro, offering a promising tool for targeted cancer therapy.

Keywords:
Anionic cholesterolAnionic lipoplexesGene delivery to tumorPegylated lipoplexespH-sensitive lipoplexes

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Area of Science:

  • Nanotechnology
  • Gene Therapy
  • Biochemistry

Background:

  • Developing effective gene delivery systems is crucial for targeted cancer therapy.
  • Nanoparticles offer potential for improved drug and gene delivery.
  • Controlling nanoparticle properties like charge and pH sensitivity is key for efficacy.

Purpose of the Study:

  • To design long-circulating, pH-sensitive nanoparticles for gene delivery to tumors.
  • To create anionic pegylated lipoplexes by combining cationic lipoplexes and pegylated anionic liposomes.
  • To optimize the lipid ratio for pH-sensitive complex formation within a specific pH range.

Main Methods:

  • Formulation of anionic pegylated lipoplexes from cationic lipoplexes and pegylated anionic liposomes.
  • Monitoring particle surface charge neutralization via light scattering as a function of pH.
  • Assessing DNA compaction using DNA accessibility to picogreen.
  • Evaluating in vitro transfection efficiency and pH sensitivity using bafilomycin.

Main Results:

  • Anionic pegylated lipoplexes were successfully prepared and demonstrated pH sensitivity between pH 5.5-6.5.
  • Optimized lipid ratios resulted in particles sensitive to pH changes relevant to tumor microenvironments.
  • DNA compaction within the lipoplexes was confirmed.
  • In vitro studies showed effective transfection and confirmed pH-sensitive properties.

Conclusions:

  • Anionic pegylated lipoplexes represent a viable strategy for pH-sensitive gene delivery.
  • These nanoparticles exhibit potential for targeted delivery to tumor sites.
  • The developed formulation shows promise for advancing cancer gene therapy applications.