Effect of lipid headgroup charge and pH on the stability and membrane insertion potential of calcium condensed gene complexes

Langmuir : the ACS Journal of Surfaces and Colloids
Nabil A AlhakamyPrajnaparamita Dhar

Abstract

Noncovalently condensed complexes of genetic material, cell penetrating peptides (CPPs), and calcium chloride present a nonviral route to improve transfection efficiency of nucleic acids (e.g., pDNA and siRNA). However, the exact mechanisms of membrane insertion and delivery of macromolecule complexes to intracellular locations as well as their stability in the intracellular environment are not understood. We show that calcium condensed gene complexes containing different hydrophilic (i.e., dTAT, K9, R9, and RH9) and amphiphilic (i.e., RA9, RL9, and RW9) CPPs formed stable cationic complexes of hydrodynamic radii 100 nm at neutral pH. However, increasing the acidity caused the complexes to become neutral or anionic and increase in size. Using zwitterionic and anionic phospholipid monolayers as models that mimic the membrane composition of the outer leaflet of cell membranes and intracellular vesicles and pHs that mimic the intracellular environment, we study the membrane insertion potential of these seven gene complexes (CPP/pDNA/Ca(2+) complexes) into model membranes. At neutral pH, all gene complexes demonstrated the highest insertion potential into anionic phospholipid membranes, with complexes containing amphiphilic peptide...Continue Reading

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Citations

Oct 16, 2015·Journal of Drug Targeting·Ly PärnasteÜlo Langel
Jun 3, 2016·Regenerative Biomaterials·Xiaochun XuXiangdong Kong
Jul 8, 2015·Journal of Controlled Release : Official Journal of the Controlled Release Society·Kshitij GuptaBruce A Shapiro
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Feb 3, 2018·Langmuir : the ACS Journal of Surfaces and Colloids·Matías A ViaNatalia Wilke
Mar 14, 2019·Molecular Pharmaceutics·Nabil A Alhakamy, Cory J Berkland
Jul 28, 2020·Biochimica Et Biophysica Acta. Biomembranes·Luis Benito Pérez Socas, Ernesto Esteban Ambroggio
Nov 16, 2021·ACS Biomaterials Science & Engineering·Patrick D MathewsOmar Mertins

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