Bringing Macromolecules into Cells and Evading Endosomes
by Oxidized Carbon Nanoparticles
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Abstract
A great challenge exists in finding
safe, simple, and effective delivery strategies to bring matters across
cell membrane. Popular methods such as viral vectors, positively charged
particles and cell penetrating peptides possess some of the following
drawbacks: safety issues, lysosome trapping, limited loading capacity,
and toxicity, whereas electroporation produces severe damages on both
cargoes and cells. Here, we show that a serendipitously discovered,
relatively nontoxic, water dispersible, stable, negatively charged,
oxidized carbon nanoparticle, prepared from graphite, could deliver
macromolecules into cells, without getting trapped in a lysosome.
The ability of the particles to induce transient pores on lipid bilayer
membranes of cell-sized liposomes was demonstrated. Delivering 12-base-long
pyrrolidinyl peptide nucleic acids with d-prolyl-(1<i>S</i>,2<i>S</i>)-2-aminocyclopentanecarboxylic acid
backbone (acpcPNA) complementary to the antisense strand of the NF-κB
binding site in the promoter region of the <i>Il6</i> gene
into the macrophage cell line, RAW 264.7, by our particles resulted
in an obvious accumulation of the acpcPNAs in the nucleus and decreased <i>Il6</i> mRNA and IL-6 protein levels upon stimulation. We anticipate
this work to be a starting point in a new drug delivery strategy,
which involves the nanoparticle that can induce a transient pore on
the lipid bilayer membrane