BackgroundMultidrug resistance-associated protein 1 (MRP1) overexpression plays a major role in chemoresistance in glioblastoma multiforme (GBM) contributing to its notorious deadly nature. Although MRP1-siRNA transfection to GBM in vitro has been shown to sensitise the cells to drug, MRP1 silencing in vivo and the phenotypic influence on the tumour and normal tissues upon MRP1 down-regulation have not been established. Here, porous silicon nanoparticles (pSiNPs) that enable high-capacity loading and delivery of siRNA are applied in vitro and in vivo.ResultWe established pSiNPs with polyethyleneimine (PEI) capping that enables high-capacity loading of siRNA (92 µg of siRNA/mg PEI-pSiNPs), and optimised release profile (70% released between 24 and 48 h). These pSiNPs are biocompatible, and demonstrate cellular uptake and effective knockdown of MRP1 expression in GBM by 30%. Also, siRNA delivery was found to significantly reduce GBM proliferation as an associated effect. This effect is likely mediated by the attenuation of MRP1 transmembrane transport, followed by cell cycle arrest. MRP1 silencing in GBM tumour using MRP1-siRNA loaded pSiNPs was demonstrated in mice (82% reduction at the protein level 48 h post-injection), and it also produced antiproliferative effect in GBM by reducing the population of proliferative cells. These results indicate that in vitro observations are translatable in vivo. No histopathological signs of acute damage were observed in other MRP1-expressing organs despite collateral downregulations.ConclusionsThis study proposes the potential of efficient MRP1-siRNA delivery by using PEI-capped pSiNPs in achieving a dual therapeutic role of directly attenuating the growth of GBM while sensitising residual tumour cells to the effects of chemotherapy post-resection.Electronic supplementary materialThe online version of this article (10.1186/s12951-018-0365-y) contains supplementary material, which is available to authorized users.
Simple molecular structures capable of emitting over the entire visible range are still a challenge. Planar molecular structures have the drawback of fluorescence quenching in the solid state thus limiting their application fields. Combining long range excimer/exciplex emissions with a compound emission have been used to get white light. In this work, a series of new coumarin derivatives having a planar structure have been synthesized and characterized. The effects of systematic variation in alkyl chain functionalization providing morphological variations that permit interesting solid state emitting properties have been discussed simultaneously with electrochemical behavior and OLED (organic light emitting diode) device applications. Carbon chains containing 0-16 carbon atoms have been studied in order to conclude the results that systematic changes in alkyl group substitution can be utilized as a tool to tune the emitting color of these planar coumarins. Alkyl chains were introduced by O-acylation and O-benzoylation reaction on the hydroxyl group of parent coumarin 5. Thus the present strategy is also helpful in establishing a template to control the unproductive interchromophore electronic couplings.Solid state fluorescence properties support the crystal studies. Theoretical studies are also in agreement with experimental data. Electroluminescence of Device 2 with a turn on voltage (V on ) around 5-6 V having s-CBP doped with 1% of 8 having alkyl substitution of 2-carbons is found to exhibit white emission with CIE co-ordinates of (0.29, 0.34) which is close to white emission while the alkyl substitution of 14-carbons (compound 17) in Device 7 (V on ¼ 7 V) exhibited green emission. Thus a strategy helpful to tune the electroluminescence has been discussed.
This report deals with the fabrication and utilization of a novel 2D zinc-based metal−organic framework (MOF) {[Zn(PA 2− )(4,4′-bpy)]-(H 2 O)} n (where PA = pamoic acid and 4,4′-bpy = 4,4′-bipyridine). The Zn-MOF has been synthesized via a solvothermal method and emanates green fluorescence. As Cr(VI) is a fatal and carcinogenic ion, it is extremely important to discern and remove it from nature. The bright green fluorescence of Zn-MOF can be quenched upon interaction with a Cr 2 O 7 2− ion, which implies the MOF's applicability as a Cr(VI) detector through turn-off fluorescence signaling. On the contrary, among various strategies to remove Cr(VI), the photocatalytic reduction of Cr(VI) to Cr(III) is acknowledged as the most effective one. Delightfully, apart from being a Cr(VI) sensor, this same Zn-MOF can be further recruited as a photocatalyst to convert Cr(VI) to Cr(III). The catalytic reduction is triggered by natural sunlight, acidic pH, and a hole scavenger. In addition, good stability and reusability of the Zn-MOF satisfies the quest for a potential photocatalyst for conversion of Cr(VI) to Cr(III). The limit of detection for fluorometric recognition of Cr(VI) was found to be 4.12 μM, and almost a complete reduction of toxic Cr(VI) ion was achieved.
Structure-interaction/fluorescence relationship studies led to the development of a small chemical library of Zn(2+)-specific cysteamine-based molecular probes. The probe L5 with higher excitation/emission wavelengths, which absorbs in the visible region and emits in the green, was chosen as a model imaging material for biological studies. After successful imaging of intracellular zinc in four different kinds of cells including living organisms, plant, and animal cells, in vivo imaging potential of L5 was evaluated using plant systems. In vivo imaging of translocation of zinc through the stem of a small herb with a transparent stem, Peperomia pellucida, confirmed the stability of L5 inside biological systems and the suitability of L5 for real-time analysis. Similarly, fluorescence imaging of zinc in gram sprouts revealed the efficacy of the probe in the detection and localization of zinc in cereal crops. This imaging technique will help in knowing the efficiency of various techniques used for zinc enrichment of cereal crops. Computational analyses were carried out to better understand the structure, the formation of probe-Zn(2+) complexes, and the emission properties of these complexes.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.