Silica nanoparticles of microrods enter lung epithelial cells

Abstract

A novel type of microparticle has recently been engineered. It consists of amorphous silica nanoparticles and has a corncob-like shape. It has already been demonstrated in vivo that alveolar macrophages in the lung are able to engulf this particulate carrier and that it also functions successfully as a gene delivery system. This subsequently raises the question as to whether epithelial cells may also be possible targets for these microrods. For this purpose, the alveolar epithelial cell line A549 was used presently. The epithelial character of these confluent cells was documented by the presence of tight junctions using a freeze-fracture technique and transmission electron microscopy. A toxic effect of the particles incubated with these cells was largely excluded. The interaction of the microparticles with the epithelial cells was observed using confocal microscopy and live cell imaging. Interestingly, the particles entered the epithelial cells within hours. After 1 day, the intracellular particles began to disaggregate and release the silica nanoparticles. Thus, even epithelial cells may serve as targets for this novel carrier and gene delivery system. This is particularly important since safe and effective gene delivery remains an unsolved problem. In addition, delivery of anti-cancer and anti-infective drugs may be an application of this novel particulate carrier.

Nanostructured Microparticles Repolarize Macrophages and Induce Cell Death in an In Vitro Model of Tumour-Associated Macrophages

“…Because of the lack of activation of hTLR2 cells and no responsiveness in the recombinant factor C assay (showing absence of LPS/TLR4 activation), we could exclude that the inflammatory cell activation exhibited by µRs is facilitated due to a contamination with bacterial cell wall/membrane component agonists. To investigate whether the detected cell activation is dependent on microparticle integrity, disintegrated µRs were employed [ 16 ], but the activating potential of intact and disintegrated µRs was similar. Silica nanoparticles resulted in a slightly higher inflammatory cell activation than the other raw materials employed for µR synthesis, i.e., the coating substances dextran sulphate (DS) and branched polyethyleneimine (PEI), which showed no activity.…”

“…Nine different µR batches were analysed in concentrations as used for treatments (100 and 200 µg/mL) in three different experiments. Because µRs are expected to disintegrate within hours in culture media [ 16 ], disintegrated µRs were also analysed. In each experiment, spike controls with exogenous LPS (0.05 EU/mL) were included (accepted recovery rate 50–200% as recommended by the manufacturer).…”

“…In vitro, we showed successful delivery of siRNA against TNF to macrophage-like THP-1 cells resulting in anti-inflammatory effects [ 15 ]. In contrast, the A549 alveolar epithelial-like cancer cell line did not take up the intact particles [ 16 ]. Degradation products were taken up independent from cell type starting after 3–6 h. After 48 h, many µRs were disintegrated into nanoparticles.…”

A novel laboratory-based strategy for single adipocyte and adipose-derived stem cells extraction for transplantation: an experimental research

“…The morphology of the adipocytes was observed under the microscope. Cell mask red (20) and DAPI (21) double staining were used to check whether the adipocytes in the single-cell suspension were structurally complete.…”

Aspherical, Nano-Structured Drug Delivery System with Tunable Release and Clearance for Pulmonary Applications

“…Particles with high aspect ratios are taken up more slowly and in fewer amounts [ 38 , 39 ], resulting in reduced clearance for an extended release and absorption time. Additionally, for nano-in-micro carriers, non-cleared rods start to break down, allowing the resulting, free nano-particles to engage with immunologically active epithelial cells [ 40 ].…”