Revisiting the impacts of silica nanoparticles on endothelial cell junctions and tumor metastasis

•m-SiO2-PEG shows less destruction to the vascular system than f-SiO2•m-SiO2-PEG intravasation and extravasation prevents cancer cells from migrating upon intracellular endocytosis The fast-growing investigations of mesoporous silica (m-SiO2) have been offering great opportunities for nanomedicine. Recently, highly agglomerated fumed (f-SiO2) sintered by elevated temperatures without any surface modification has suggested cause severe endothelial leakiness, which promotes metastasis. Nevertheless, we demonstrate that excellently dispersed m-SiO2 decorated with PEG (m-SiO2-PEG) exhibits negligible destructiveness toward cell junctions leads no significant effects on tumor metastasis in comparison f-SiO2. More importantly, well-dispersed m-SiO2-PEG is capable effectively preventing endocytosis. current study verifies properly surface-modified NPs could lead damage system, guarantees can be used safely as an important component Inorganic nanoparticles received attention medical field. 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Mesopor. 161: 160-167https://doi.org/10.1016/j.micromeso.2012.05.035Crossref (56) Up until now, almost all m-SiO2-based nanosystems biocompatibility. NP’s chemistry affecting behavior junctions, herein revisit subject try evidence reasonably commonly accepted way. detail, chose three models—fumed (f-SiO2), m-SiO2, PEG-modified (m-SiO2-PEG)—to reveal nanomaterials, influences caused adhering junction VE-cadherin complex. better understand elucidate mechanism possible disruption 60 ns molecular dynamics (MD) simulation. theoretical calculation that, compared unmodified SiO2, substantially weakened impact VE-cadherin. induce f-SiO2 minimize gaps penetrating mild van der Waals electrostatic interactions. largely inhibited (Scheme 1). much adhesion VE vitro. addition, fewer suppressing cells’ following thanks charging, chemistry. Importantly, conventional possess immune systems models. Moreover, selected verify NP junctions. adopted (f-SiO2, m-SiO2-PEG) investigate behaviors. fabricated via flame pyrolysis SiCl4 according equation + 2H2 O2 → 4HCl. carried out under ultrahigh temperature 1,200°C–1,400°C followed thermal quenching (Figure 1A), evaporation hydrolysis produced Si(OH)4, Si(OH)4 condensation seeds branched chainlike particles. plentiful dispersity. meantime, general 95°C, where tetraethyl orthosilicate (TEOS) source co-hydrolyzed triethanolamine (TEA) alkalic catalyzer cetyltrimethylammonium chloride (CTAC) surfactant template 1B). 60°C 1C). transmission electron microscopy (TEM) image particles 1D), whereas as-prepared sphere structure 1E). Energy dispersive X-ray spectroscopy (EDS) profiles confirm Si O elements S1). Benefiting steric hindrance chains, methoxy chains endows colloidal stability physiological conditions. zeta negative approximately −10 mV, slightly lower, proving decreased density groups. sample increased 1F) enlarged hydrated diameter light scattering (DLS) technique S2) weights PEG, surface. Specific functional analyzed Fourier transform infrared (FTIR) spectroscopy, FTIR spectra display absorption peak 2,887 cm−1, attributed stretching vibration –CH2– framework demonstrating successful (Figures 1G S3). Thermogravimetric prove 1H). first step (30°C ∼ 100°C) mass loss associated removal adsorbed water molecules, second (100°C 300°C) silanol group Figure S4 silicon reduced step. third (300°C 800°C) originates decomposition PEG. characterized production behaviors reactive oxygen species (ROS) differently NPs. Methylene blue (MB) decolorization assays applicable colorimetric determination ROS. checked MB degradation various intervals. unable trigger Meanwhile, precise oxide qualitatively elucidated paramagnetic resonance (EPR) spectroscopy. 5,5-Dimethyl-1-pyrroline N-oxide (DMPO) typical spin-trapping agent ⋅OH. Clearly, signals radicals detected either group, shown S5. conclusion, experimental results, hardly produce ROS, due fact ternary ring gaseous unstable aqueous solution. Hence, not ROS but status different ways TEM elemental mapping (f-TiO2) strong agglomeration, (c-TiO2) mark S6 S7). potentials, spectra, thermogravimetric analysis (TGA) c-TiO2 (c-TiO2-PEG) samples S8). conducted Our indeed red (RBC) lysis; however, fortunately enough, membrane damages same concentration (200 μg mL−1), S9. means behavior, dependent Functioning cadherin, pivotal maintaining intercellular ensure cohesion integrity solid barrier.10Setyawati whether will introduced MD simulations theoretically predict NP-VE-cadherin simulation probe linkage m-SiO2-PEG. One, two, four (marked [SiO2]1, [SiO2]2, [SiO2]4, respectively) one, SiO2-PEG [SiO2-PEG]1, [SiO2-PEG]2, [SiO2-PEG]4, allowed instantaneously approach interact double complex in-junction 2A). root-mean-square deviation (RMSD) changes atomic positions varied numbers plotted against time 2B). intensified grew, elucidating structural course. showed diminished unnoticeable variations, PEGylat