2 research outputs found
Shape Effect on Particle-Lipid Bilayer Membrane Association, Cellular Uptake, and Cytotoxicity
Although computer simulation and
cell culture experiments have shown that elongated spherical particles
can be taken up into cells more efficiently than spherical particles,
experimental investigation on effects of these different shapes over
the particle–membrane association has never been reported.
Therefore, whether the higher cellular uptake of an elongated spherical
particles is a result of a better particle–membrane association
as suggested by some calculation works or a consequence of its influence
on other cellular trans-membrane components involved in particle translocation
process, cannot be concluded. Here, we study the effect of particle
shape on the particle–membrane interaction by monitoring the
association between particles of various shapes and lipid bilayer
membrane of artificial cell-sized liposomes. Among the three shaped
lanthanide-doped NaYF<sub>4</sub> particles, all with high shape purity
and uniformity, similar crystal phase, and surface chemistry, the
elongated spherical particle shows the highest level of membrane association,
followed by the spherical particle with a similar radius, and the
hexagonal prism-shaped particle, respectively. The free energy of
membrane curvature calculated based on a membrane indentation induced
by a particle association indicates that among the three particle
shapes, the elongated spherical particle give the most stable membrane
curvature. The elongated spherical particles show the highest cellular
uptake into cytosol of human melanoma (A-375) and human liver carcinoma
(HepG2) cells when observed through a confocal laser scanning fluorescence
microscope. Quantitative study using flow cytometry also gives the
same result. The elongated spherical particles also possess the highest
cytotoxicity in A-375 and normal skin (WI-38) cell lines, comparing
to the other two shaped particles
Bringing Macromolecules into Cells and Evading Endosomes by Oxidized Carbon Nanoparticles
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