Jiraporn Seemork

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 NaYF4 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-(1S,2S)-2-aminocyclopentanecarboxylic acid backbone (acpcPNA) complementary to the antisense strand of the NF-κB binding site in the promoter region of the Il6 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 Il6 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.

Penetration of Oxidized Carbon Nanospheres through Lipid Bilayer Membrane: Comparison to Graphene Oxide and Oxidized Carbon Nanotubes, and Effects of pH and Membrane Composition

Here we show that the ability of oxidized carbon particles to penetrate phospholipid bilayer membrane varies with the particle shapes, chemical functionalities on the particle surface, lipid compositions of the membrane and pH conditions. Among the similar surface charged oxidized carbon particles of spherical (oxidized carbon nanosphere, OCS), tubular (oxidized carbon nanotube, OCT), and sheet (oxidized graphene sheet, OGSh) morphologies, OCS possesses the highest levels of adhesion to lipid bilayer membrane and penetration into the cell-sized liposome. OCS preferably binds better to the disordered lipid bilayer membrane (consisting of 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine) as compared to the ordered membrane (consisting of 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine and cholesterol). The process of OCS-induced leak on the membrane is pH responsive and most pronounced under an acidic condition. Covalently decorating the OCSs surface with poly(ethylene oxide) or (2-aminoethyl)trimethylammonium moieties decreases its ability to interact with the membrane. When used as carriers, OCSs can deliver curcumin into nucleus of A549 human lung cancer and human embryonic kidney cells, in contrast, curcumin molecules delivered by OCTs remain in the cytoplasm. OGShs cannot significantly enter cells and cannot induce noticeable cellular uptake of curcumin.

Rheological response under nonisothermal stretching for immiscible blends of isotactic polypropylene and acrylate polymer

The addition of acrylate polymers with low molecular weight, such as poly(isobutyl methacrylate) (PIBM) and poly(methyl methacrylate) (PMMA), effectively enhances the force required to stretch a molten polypropylene (PP) at the nonisothermal condition without the enhancement of shear viscosity in the molten state. The mechanism of this phenomenon is found to be attributed to prompt solidification of PIBM and PMMA droplets, which deform greatly to the flow direction in the die land and near the die exit during the extrusion and stretching processes. After the die exit, the deformed droplets show the glassification prior to the crystallization of PP matrix because of the rapid cooling at stretching. Consequently, they behave like rigid fibers in a molten PP, which provide the excess stress by large shear deformation of the matrix between the dispersed glassy fibers during stretching.