Monthly Archive for: ‘September, 2016’

Nanostickers for cells: a model study using cell–nanoparticle hybrid aggregates

Nanostickers for cells: a model study using cell–nanoparticle hybrid aggregates

B. Brunel, G. Beaune, U. Nagarajana, S. Dufour, F. Brochard-Wyart and F. M. Winnik.

We present direct evidence that nanoparticles (NPs) can stick together cells that are inherently non-adhesive. Using cadherin-depleted S180 murine cells lines, which exhibit very low cell–cell adhesion, we show that NPs can assemble dispersed single cells into large cohesive aggregates. The dynamics of aggregation, which is controlled by diffusion and collision, can be described as a second-order kinetic law characterized by a rate of collision that depends on the size, concentration, and surface chemistry of the NPs. We model the cell–cell adhesion induced by the “nanostickers” using a three-state dynamical model, where the NPs are free, adsorbed on the cell membrane or internalized by the cells. We define a “sticking efficiency parameter” to compare NPs and look for the most efficient type of NP. We find that 20 nm carboxylated polystyrene NPs are more efficient nanostickers than 20 nm silica NPs which were reported to induce fast wound healing and to glue soft tissues. Nanostickers, by increasing the cohesion of tissues and tumors, may have important applications for tissue engineering and cancer treatment. Link to the article.

Membrane Translocation and Organelle-Selective Delivery Steered by Polymeric Zwitterionic Nanospheres

Membrane Translocation and Organelle-Selective Delivery Steered by Polymeric Zwitterionic Nanospheres

N. Morimoto, M. Wakamura, K. Muramatsu, S. Toita, M. Nakayama, W. Shoji, M. Suzuki, F. M. Winnik.

The majority of nanoparticles designed for cellular delivery of drugs and imaging agents enter the cell via endocytotic pathways leading to their entrapment in endosomes that present a robust barrier to further trafficking of the nanoparticles within the cells. A few materials, such as the cell penetrating peptides (CPPs), are known to enter cells not only via endocytosis, but also via translocation through the cell membrane into the cytoplasm, successfully bypassing the endosomes. We report here that random copolymers of 3-dimethyl(methacryloyloxyethyl)ammonium propanesulfonate and poly(ethylene glycol) methacrylate, p(DMAPS-ran-PEGMA), are internalized in cells primarily via translocation through the cell membrane rather than endocytosis. The properties of the polymers and their modes of uptake were investigated systematically by dynamic light scattering, confocal fluorescence microscopy, and flow cytometry. Using specific inhibitors of the cellular uptake machinery in a human cervical carcinoma cell line (HeLa), we show that these nontoxic synthetic polyzwitterions exist in cell media as self-assembled nanospheres that unravel as they adsorb on the plasma membrane and translocate through it. Conjugates of p(DMAPS-ran-PEGMA) with rhodamine B were delivered selectively to the mitochondria, whereas doxorubicin (Dox)-p(DMAPS-ran-PEGMA) conjugates were accumulated in both the nucleus and the mitochondria, effectively inducing apoptosis in HeLa cells. These findings suggest that the noncytotoxic and readily synthesized p(DMAPS-ran-PEGMA) can find applications as bioimaging tools and drug nanocarriers.

Estradiol-tethered micropatterned surfaces for the study of estrogenic non-genomic pathways

Estradiol-tethered micropatterned surfaces for the study of estrogenic non-genomic pathways

B. Qi, Y. Shimizu, J. Nakanishi and F.M. Winnik.

Besides its well-known hormonal effects initiated in the nucleus, estradiol (E2) also activates non-nuclear pathways through interactions with receptors located on the cell plasma membrane. Micropatterned substrates consisting of gold dots bearing tethered E2 distributed on a cell-adhesive substrate were prepared and shown to trigger specifically E2 non-genomic effects in cells grown on the substrates.

Boron nitride nanotubes as vehicles for intracellular delivery of fluorescent drugs and probes

Boron nitride nanotubes as vehicles for intracellular delivery of fluorescent drugs and probes

J. Niskanen, I. Zhang, Y. Xue, D. Golberg, D. Maysinger, F. M. Winnik

Aim: To evaluate the response of cells to boron nitride nanotubes (BNNTs) carrying fluorescent probes or drugs in their inner channel by assessment of the cellular localization of the fluorescent cargo, evaluation of the in vitro release and biological activity of a drug (curcumin) loaded in BNNTs. Methods: Cells treated with curcumin-loaded BNNTs and stimulated with lipopolysaccharide were assessed for nitric oxide release and stimulation of IL-6 and TNF-α. The cellular trafficking of two cell-permeant dyes and a non-cell-permeant dye loaded within BNNTs was imaged. Results: BNNTs loaded with up to 13 wt% fluorophores were internalized by cells and controlled release of curcumin triggered cellular pathways associated with the known anti-inflammatory effects of the drug. Conclusion: The overall findings indicate that BNNTs can function as nanocarriers of biologically relevant probes/drugs allowing one to examine/control their local intracellular localization and biochemical effects, leading the way to applications as intracellular nanosensors./p>