No 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-(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.

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.

Drawdown force, defined as the force needed to stretch a polymer melt uniaxially at capillary extrusion, is investigated using isotactic polypropylene. In this study, we focus on the effect of die geometry on the drawdown force. As similar to the swell ratio, which decreases with increasing die length, the drawdown force is found to increase with the die length. A prolonged residence time in a long die leads to the marked orientation. Consequently, crystallization occurs rapidly after passing through a long die, which is confirmed by wide-angle X-ray measurements. Moreover, the rapid crystallization by the addition of a nucleating agent also enhances the drawdown force. C 2014 Wiley Periodicals, Inc. Adv Polym Technol 2015, 34, 21477; View this article online at wileyonlinelibrary.com.

The effects of size and shape, i.e., sphere and fiber, of dispersed poly(butylene terephthalate) (PBT) in poly(lactic acid) (PLA) matrix on the morphology and porous structure of the biaxially stretched films are comparatively investigated. Scanning electron microscope results confirm that the PBT fine fibers can be produced by melt-stretching following by fast quenching. Rheological characterization reveals the random network structure of PBT fibers. Further, the stretched films composed of spherical PBT particles show the ellipsoidal microvoids due to the interfacial debonding, and the void size relates to the particle size of PBT. However, size of PBT droplets does not influence the void content of the stretched films. The void content considerably increases for equibiaxial deformation as compared with planar deformation, particularly at high draw ratio. Additionally, the stretched films containing fibrous dispersion exhibit the nonaffine behavior and the highest void content of 8%, which is probably due to the localized deformation between fibers.

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 OCS's 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.

Release of fragrant molecules from poly(ethylene oxide) (PEO) grafted chitosan particles could be controlled in a switchable manner through the thermo‐responsive hydration/dehydration of the PEO corona of the spheres that resulted in the de‐aggregation/aggregation among particles and corresponded to an on/off fragrant release switch. In water, mPEO–chitosan self‐assembled into spherical particles with the mPEO corona covering the surface and vanillin and citral could be loaded into the particles. The mPEO–water interaction took place at temperatures lower than the lower critical solution temperature (LCST) value and resulted in de‐aggregation among spheres which enabled release of the loaded fragrance molecules, whilst mPEO–mPEO interactions occurred at temperatures higher than the LCST value and resulted in aggregation among spheres which also halted the fragrance release. This thermal switch could be tuned to a desired temperature by adjusting the salt concentration. After the release of all fragrances, the thermo‐responsive carriers could be refilled again. Copyright © 2012 John Wiley & Sons, Ltd.

The effect of crystallization on the drawdown force, i.e., the force needed to stretch a molten polymer uniaxially, was studied using conventional polyethylene samples. It was found that the drawdown force of high-density polyethylene (HDPE) increases with increasing the die length. This is attributed to the rapid crystallization owing to the low density of entanglement couplings after passing through a long die. On the contrary, the die length has no/little influence on the drawdown force of linear low-density polyethylene (LLDPE), indicating that the molecular orientation applied in a long die is almost relaxed prior to the crystallization. Even for LLDPE, however, the drawdown force becomes sensitive to the die length by the addition of a small amount of HDPE, because the crystallization process is accelerated.