Even though the administration of chemotherapeutic agents such as erlotinib is clinically established for the treatment of breast cancer, its efficiency and the therapy outcome can be greatly improved using RNA interference (RNAi) mechanisms for a combinational therapy. However, the cellular uptake of bare small interfering RNA (siRNA) is insufficient and its fast degradation in the bloodstream leads to a lacking delivery and no suitable accumulation of siRNA inside the target tissues. To address these problems, non-ionic surfactant vesicles (niosomes) were used as a nanocarrier platform to encapsulate Lifeguard (LFG)-specific siRNA inside the hydrophilic core. A preceding entrapment of superparamagnetic iron-oxide nanoparticles (FexOy-NPs) inside the niosomal bilayer structure was achieved in order to enhance the cellular uptake via an external magnetic manipulation. After verifying a highly effective entrapment of the siRNA, the resulting hybrid niosomes were administered to BT-474 cells in a combinational therapy with either erlotinib or trastuzumab and monitored regarding the induced apoptosis. The obtained results demonstrated that the nanocarrier successfully caused a downregulation of the LFG gene in BT-474 cells, which led to an increased efficacy of the chemotherapeutics compared to plainly added siRNA. Especially the application of an external magnetic field enhanced the internalization of siRNA, therefore increasing the activation of apoptotic signaling pathways. Considering the improved therapy outcome as well as the high encapsulation efficiency, the formulated hybrid niosomes meet the requirements for a cost-effective commercialization and can be considered as a promising candidate for future siRNA delivery agents.
Hydrous boehmite (γ-AlOOH) nanoparticles (BNP) show great potential as nanoscale filler for the fabrication of fiber reinforced nanocomposite materials. Notably, the particle− matrix interaction has been demonstrated to be decisive for improving the matrix-dominant mechanical properties in the past years. Tailoring the surface properties of the nanofiller enables to selectively design the interaction and thus to exploit the benefits of the nanocomposite in an optimal way. Here, an extensive study is presented on the binding of (3-aminopropyl)triethoxysilane (APTES), a common silane surface modifier, on BNP in correlation to different process parameters (concentration, time, temperature, and pH). Furthermore, a comprehensive characterization of the modified BNP was performed by using elemental analysis (EA), thermogravimetric analysis (TGA) coupled with mass spectrometry (TGA-MS), and Kaiser's test (KT). The results show an increasing monolayer formation up to a complete surface coverage with rising APTES concentration, time, and temperature, resulting in a maximal grafting density of 1.3 molecules/nm 2 . Unspecific multilayer formation was solely observed under acidic conditions. Comparison of TGA-MS results with data recorded from EA, TGA, and KT verified that TGA-MS is a convenient and highly suitable method to elucidate the ligand binding in detail.
Targeted tumor therapy can provide the basis for the inhibition of tumor growth. However, a number of toxin-based therapeutics lack efficacy because of insufficient endosomal escape after being internalized by endocytosis. To address this problem, the potential of glycosylated triterpenoids, such as SO1861, as endosomal escape enhancers (EEE) for superparamagnetic iron oxide nanoparticle (SPION)-based toxin therapy was investigated. Herein, two different SPION-based particle systems were synthesized, each selectively functionalized with either the targeted toxin, dianthin-epidermal growth factor (DiaEGF), or the EEE, SO1861. After applying both particle systems in vitro, an almost 2000-fold enhancement in tumor cell cytotoxicity compared to the monotherapy with SPION-DiaEGF and a 6.7-fold gain in specificity was observed. Thus, the required dose of the formulation was appreciably reduced, and the therapeutic window widened.
Encapsulation of iron oxide and gold nanoparticles into the bilayer structure of transferrin-modified niosomes enables greatly enhanced and contamination-free SERS-signals in vitro as well as a dual-targeting functionality towards cancer cells.
To improve the performance of lead-free piezoelectric composites, the functionalization of the filler particles has been suggested as a successful strategy in several recent reports. The details of the functionalization process, however, are not clear, nor is its influence on the dielectric properties of the composites. This study reports a systematic investigation of the functionalization process parameters of barium titanate nanoparticles (BTONP) with 3-(trimethoxysilyl)propyl methacrylate (TMSPM) used as a linker to an acrylate-based matrix polymer. Functionalization process temperature, time, functionalization agent ratio, solvent, and catalyst influence on the functionalization degree were measured by thermogravimetric analysis (TGA), elemental analysis, and Fourier-transform infrared (FTIR) spectroscopy. Elevated temperature and average functionalization time led to the highest functionalization degree in the form of a TMSPM monolayer on the particle surface. Three solvents, with and without catalysts, were investigated and two types of functionalized BTONP were selected for composite manufacturing. To this end, the functionalized particles were used to manufacture 10 vol.% BTONP/photopolymer UV light-curable composite suspensions. After solidification of the suspensions by exposure to UV light, the microstructure and dielectric properties of the resulting composites were investigated. It was seen that functionalization improves the dispersion of particles, increases suspension viscosity, and decreases the curing depth and dielectric properties.
BackgroundIn vitro and in vivo biosensing through surface-enhanced Raman scattering often suffer from signal contamination diminishing both the limit of detection and quantification. However, overcoming the lack of specificity requires excessive nanoparticle concentrations, which may lead to adverse side effects if applied to patients. ResultsWe propose encapsulation of iron oxide (FexOy) and gold (Au) nanoparticles (NPs) into the bilayer structure of transferrin-modified niosomes. This approach enables achieving greatly enhanced and contamination-free SERS-signals in vitro as well as a dual-targeting functionality towards MCF-7 breast cancer cells. An in-depth characterization of FexOyNPs- and AuNPs-loaded niosomes (AuNPs/FexOyNPs/NIO) after magnetic downstream processing reveals defined hybrid niosome structures, which show a long-term SERS-signal stability in various media such as MCF-7 cell culture medium. In vitro 2D-SERS imaging unveil a successful incorporation of a non-toxic dose of hybrid NPs into MCF-7 cells, which leads to strong and almost contamination-free SERS-signals. The measured signal-to-noise ratio of the in vitro signal exceeds the values required by DIN 32645 for the successful validation of a detection method. ConclusionsThe hybrid niosomes can be considered a promising and efficient agent for the establishment and commercialization of a highly sensitive detection kit for monitoring cancerous tissue.
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