A new and never before reported hetero-arylidene-9(10H)-anthrone structure (4) was unexpectedly isolated on reaction of 1,2-dimethyl-3-ethylimidazolium iodide (2) and 9-anthracenecarboxaldehyde (3) under basic conditions. Its structure was unequivocally confirmed by X-ray crystallography. No cytotoxicity in human healthy fibroblasts and in two different cancer cell lines was observed, indicating its applicability in biological systems. Compound 4 interacts with CT-DNA by intercalation between the adjacent base pairs of DNA with a high binding affinity [Kb = 2.0 (±0.20) × 105 m–1], which is 10 × higher than that described for doxorubicin [Kb = 3.2 (±0.23) × 104 m–1]. Furthermore, compound 4 quenches the fluorescence emission of a GelRed–CT-DNA system with a quenching constant (KSV) of 3.3 (±0.3) × 103 m–1 calculated by the Stern–Volmer equation.

Mesenchymal stem cells are multipotent adult stem cells capable of generating bone, cartilage and fat, and are thus currently being exploited for regenerative medicine. When considering osteogenesis, developments have been made with regards to chemical induction (e.g. differentiation media) and physical induction (e.g. material stiffness, nanotopography), targeting established early transcription factors or regulators such as runx2 or bone morphogenic proteins and promoting increased numbers of cells committing to osteo-specific differentiation. Recent research highlighted the involvement of microRNAs in lineage commitment and terminal differentiation. Herein, gold nanoparticles that confer stability to short single stranded RNAs were used to deliver MiR-31 antagomiRs to both pre-osteoblastic cells and primary human MSCs in vitro. Results showed that blocking miR-31 led to an increase in osterix protein in both cell types at day 7, with an increase in osteocalcin at day 21, suggesting MSC osteogenesis. In addition, it was noted that antagomiR sequence direction was important, with the 5 prime reading direction proving more effective than the 3 prime. This study highlights the potential that miRNA antagomiR-Tagged nanoparticles offer as novel therapeutics in regenerative medicine.

Despite great advances in the fight against cancer, traditional chemotherapy has been hindered by the dose dependent adverse side effects that reduce the usable doses for effective therapy. This has been associated to drug resistance in tumor cells that often cause relapse and therapy failure. These drawbacks have been tackled by combining different therapeutic regiments that prevent drug resistance while decreasing the chemotherapy dose required for efficacious ablation of cancer. In fact, new metallic compounds have been in a continuous development to extend the existing chemotherapy arsenal for these combined regimens. Here, we demonstrate that combination of a metallic compound (TS265), previously characterized by our group, with photothermy circumvents cells resistant to Doxorubicin (DOX). We first engendered a colorectal carcinoma cell line (HCT116) highly resistant to DOX, whose viability was diminished after administration of TS265. Cancer cell death was potentiated by challenging these cells with 14 nm spherical gold nanoparticles followed by laser irradiation at 532 nm. The combination of TS265 with photothermy lead to 65% cell death of the DOX resistant cells without impacting healthy cells. These results support the use of combined chemotherapy and photothermy in the visible spectrum as an efficient tool for drug resistant tumors.

Many diseases have their treatment options narrowed and end up being fatal if detected during later stages. As a consequence, point-of-care devices have an increasing importance for routine screening applications in the health sector due to their portability, fast analyses and decreased cost. For that purpose, a multifunctional chip was developed and tested using gold nanoprobes to perform RNA optical detection inside a microfluidic chip without the need of molecular amplification steps. As a proof-of-concept, this device was used for the rapid detection of chronic myeloid leukemia, a hemato-oncological disease that would benefit from early stage diagnostics and screening tests. The chip passively mixed target RNA from samples, gold nanoprobes and saline solution to infer a result from their final colorimetric properties. An optical fiber network was used to evaluate its transmitted spectra inside the chip. Trials provided accurate output results within 3 min, yielding signal-to-noise ratios up to 9 dB. When compared to actual state-of-art screening techniques of chronic myeloid leukemia, these results were, at microscale, at least 10 times faster than the reported detection methods for chronic myeloid leukemia. Concerning point-of-care applications, this work paves the way for other new and more complex versions of optical based genosensors.

Photothermal Therapy (PTT) impact in cancer therapy has been increasing due to the enhanced photothermal capabilities of a new generation of nanoscale photothermal agents. Among these nanoscale agents, gold nanoshells and nanorods have demonstrated optimal properties for translation of near infra-red radiation into heat at the site of interest. However, smaller spherical gold nanoparticles (AuNPs) are easier to produce, less toxic and show improved photoconversion capability that may profit from the irradiation in the visible via standard surgical green lasers. Here we show the efficient light-to-heat conversion of spherical 14 nm AuNPs irradiated in the visible region (at the surface plasmons resonance peak) and its application to selectively obliterate cancer cells. Using breast cancer as model, we show a synergistic interaction between heat (photoconversion at 530 nm) and cytotoxic action by doxorubicin with clear advantages to those of the individual therapy approaches.

Digital microfluidics (DMF) arises as the next step in the fast-evolving field of operation platforms for molecular diagnostics. Moreover, isothermal schemes, such as loop-mediated isothermal amplification (LAMP), allow for further simplification of amplification protocols. Integrating DMF with LAMP will be at the core of a new generation of detection devices for effective molecular diagnostics at point-of-care (POC), providing simple, fast, and automated nucleic acid amplification with exceptional integration capabilities. Here, we demonstrate for the first time the role of coupling DMF and LAMP, in a dedicated device that allows straightforward mixing of LAMP reagents and target DNA, as well as optimum temperature control (reaction droplets undergo a temperature variation of just 0.3°C, for 65°C at the bottom plate). This device is produced using low-temperature and low-cost production processes, adaptable to disposable and flexible substrates. DMF-LAMP is performed with enhanced sensitivity without compromising reaction efficacy or losing reliability and efficiency, by LAMP-amplifying 0.5 ng/µL of target DNA in just 45 min. Moreover, on-chip LAMP was performed in 1.5 µL, a considerably lower volume than standard bench-top reactions.

Ion sensitive field-effect transistors (ISFET) are the basis of radical new sensing approaches. Reliable molecular characterization of specific detection of DNA and/or RNA is vital for disease diagnostics and to follow up alterations in gene expression profiles. Devices and strategies for biomolecular recognition and detection should be developed into reliable and inexpensive platforms. Here, we describe the development of a flexible thin-film sensor for label free gene expression analysis. A charge modulated ISFET based sensor was integrated with real-time DNA/RNA isothermal nucleic acid amplification: Loop-mediated isothermal amplification (LAMP) and Rolling Circle Amplification (RCA) techniques for c-MYC and BCR-ABL1 genes, allowing for the real-time quantification of template. Also, RCA allowed the direct quantification of RNA targets at room temperature, eliminating the requirement for external temperature controllers and overall complexity of the molecular diagnostic approach. This integration between the biological and the sensor/electronic approaches enabled the development of an inexpensive and direct gene expression-profiling platform.

Gene therapy arises as a great promise for cancer therapeutics due to its potential to silence genes involved in tumor development. In fact, there are some pivotal gene drivers that suffer critical alterations leading to cell transformation and ultimately to tumor growth. In this vein, gene silencing has been proposed as an active tool to selectively silence these molecular triggers of cancer, thus improving treatment. However, naked nucleic acid (DNA/RNA) sequences are reported to have a short lifetime in the body, promptly degraded by circulating enzymes, which in turn speed up elimination and decrease the therapeutic potential of these drugs. The use of nanoparticles for the effective delivery of these silencers to the specific target locations has allowed researchers to overcome this issue. Particularly, gold nanoparticles (AuNPs) have been used as attractive vehicles for the target-specific delivery of gene-silencing moieties, alone or in combination with other drugs. We shall discuss current trends in AuNP-based delivery of gene-silencing tools, considering the promising road ahead without overlooking existing concerns for their translation to clinics.

Digital Microfluidics (DMF) has emerged as a disruptive methodology for the control and manipulation of low volume droplets. In DMF, each droplet acts as a single reactor, which allows for extensive multiparallelization of biological and chemical reactions at a much smaller scale. DMF devices open entirely new and promising pathways for multiplex analysis and reaction occurring in a miniaturized format, thus allowing for healthcare decentralization from major laboratories to point-of-care with accurate, robust and inexpensive molecular diagnostics. Here, we shall focus on DMF platforms specifically designed for nucleic acid amplification, which is key for molecular diagnostics of several diseases and conditions, from pathogen identification to cancer mutations detection. Particular attention will be given to the device architecture, materials and nucleic acid amplification applications in validated settings.

Gold nanoparticles, due to their unique physicochemical properties, are among the most widely used nanoscale-based platforms for molecular diagnostics. The intrinsic chemical stability and apparent lack of toxicity have also prompted for application in therapeutics, e.g., for imaging modalities and as vectorization strategies for molecular modulators, i.e., gene silencing, specific targeting of cellular pathways, etc. Because of their common molecular ground, these approaches have been synergistically coupled together into molecular theranostic systems that allow for radical new in vivo diagnostics modalities with simultaneous tackling of molecular disequilibria leading to disease. Despite this tremendous potential, gold nanoparticle- based systems still have to make their effective translation to the clinics. This chapter focuses on the use of gold nanoparticles for molecular diagnostics and molecular therapeutics and their application in theranostics. Attention is paid to those systems that have moved toward the clinics.

Due to their small size and unique properties, multifunctional nanoparticles arise as versatile delivery systems easily grafted with a vast array of functional moieties, such as anticancer cytotoxic chemotherapeutics and targeting agents. Here, we formulated a multifunctional gold-nanoparticle (AuNP) system composed of a monoclonal antibody against epidermal growth factor receptor (EGFR) (anti-EGFR D-11) for active targeting and a Co(II) coordination compound [CoCl(H2O)(phendione)2][BF4] (phendione = 1,10-phenanthroline-5,6-dione) (TS265) with proven antiproliferative activity towards cancer cells (designated as TargetNanoTS265). The efficacy of this nanoformulation, and the non-targeted counterpart (NanoTS265), were evaluated in vitro using cancer cell models and in vivo using mice xenografts. Compared to the free compound, both nanoformulations (TargetNanoTS265 and NanoTS265) efficiently delivered the cytotoxic cargo in a controlled selective manner due to the active targeting, boosting tumor cytotoxicity. Treatment of HCT116-derived xenografts tumors with TargetNanoTS265 led to 93% tumor reduction. This simple conceptual nanoformulation demonstrates the potential of nanovectorization of chemotherapeutics via simple assembly onto AuNPs of BSA/HAS-drug conjugates that may easily be expanded to suit other cargo of novel compounds that require optimized controlled delivery to cancer target.

Due to their relevance as disease biomarkers and for diagnostics, screening of single nucleotide polymorphism (SNPs) requires simple and straightforward strategies capable to provide results in medium throughput settings. Suitable approaches relying on isothermal amplification techniques have been evolving to substitute the cumbersome and highly specialized PCR amplification detection schemes. Nonetheless, identification of an individual's genotype still requires sophisticated equipment and laborious methods. Here, we present a low-cost and reliable approach based on the allele specific loop-mediated isothermal amplification (AS-LAMP) coupled to ssDNA functionalized gold nanoparticle (Au-nanoprobe) colorimetric sequence discrimination. The Au-nanoprobe integration allows for the colorimetric detection of AS-LAMP amplification product that can be easily interpreted in less than 15 min. We targeted a clinical relevant SNP responsible for lactose intolerance (-13910C/T dbSNP rs#: 4988235) to demonstrate its proof of concept and full potential of this novel approach.

Nanotechnology has become a powerful approach to improve the way we diagnose and treat cancer. In particular, nanoparticles (NPs) possess unique features for enhanced sensitivity and selectivity for earlier detection of circulating cancer biomarkers. In vivo, NPs enhance the therapeutic efficacy of anticancer agents when compared with con-ventional chemotherapy, improving vectorization and delivery, and helping to overcome drug resistance. Nanomedicine has been mostly focused on solid cancers due to take advantage from the enhanced permeability and retention (EPR) effect experienced by tissues in the close vicinity of tumors, which enhance nanomedicine's accumulation and, consequently, improve efficacy. Nanomedicines for leukemia and lymphoma, where EPR effect is not a factor, are addressed differently from solid tumors. Nevertheless, NPs have provided innovative approaches to simple and non-invasive methodologies for diagnosis and treatment in liquid tumors. In this review, we consider the state of the art on different types of nanoconstructs for the management of liquid tumors, from preclinical studies to clinical trials. We also discuss the advantages of nanoplatforms for theranostics and the central role played by NPs in this combined strategy.

Background: Despite continuous efforts, the treatment of canine cancer has still to deliver effective strategies. For example, traditional chemotherapy with doxorubicin and/or docetaxel does not significantly increase survival in dogs with canine mammary tumors (CMTs). Aims: Evaluate the efficiency of two metal compounds [Zn(DION)2]Cl (TS26

Lung cancer is the leading cause of cancer-related mortality in the world, non-small lung cancer (NSCLC) is the most frequent subtype (85% of the cases). Within this subtype, adenocarcinoma and squamous cell carcinoma are the most frequent. New therapeutic strategies based on targeted delivery of drugs have relied on the use of biomarkers derived from the patients’ molecular profiling. Several biomarkers have been found to be useful for use as targets for precision therapy in NSCLC, such as mutations in the epidermal growth factor receptor, v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog, anaplastic lymphoma kinase, mesenchymal-epithelial transition factor receptor tyrosine kinase, BRAF, c-ros oncogene 1, P53 and phosphatase with tensin homology. Current developments in Nanomedicine have allowed for multifunctional systems capable of delivering therapeutics with increased precision to the target site/tissue, while simultaneously assisting in diagnosis. Here, we review the use of biomarkers in nanotechnology translation in NSCLC management.

Tin complexes demonstrate antiproliferative activities in some case higher than cisplatin, with IC50 at the low micromolar range. We have previously showed that the cyclic trinuclear complex of Sn(IV) bearing an aromatic oximehydroxamic acid group [nBu(2)Sn(L)](3) (L=N,2-dihydroxy-5-[N-hydroxyethanimidoyl]benzamide) (MG85) shows high anti-proliferative activity, induces apoptosis and oxidative stress, and causes destabilization of tubulin microtubules, particularly in colorectal carcinoma cells. Despite the great efficacy towards cancer cells, this complex still shows some cytotoxicity to healthy cells. Targeted delivery of this complex specifically towards cancer cells might foster cancer treatment.MG85 complex was encapsulated into liposomal formulation with and without an active targeting moiety and cancer and healthy cells cytotoxicity was evaluated.Encapsulation of MG85 complex in targeting PEGylated liposomes enhanced colorectal carcinoma (HCT116) cancer cell death when compared to free complex, whilst decreasing cytotoxicity in non-tumor cells. Labeling of liposomes with Rhodamine allowed assessing internalization in cells, which showed significant cell uptake after 6 h of incubation. Cetuximab was used as targeting moiety in the PEGylated liposomes that displayed higher internalization rate in HCT116 cells when compared with non-targeted liposomes, which seems to internalize via active binding of Cetuximab to cells.The proposed formulation open new avenues in the design of innovative transition metal-based vectorization systems that may be further extended to other novel metal complexes towards the improvement of their anti-cancer efficacy, which is usually hampered by solubility issues and/or toxicity to healthy tissues.

The limitations of platinum complexes in cancer treatment have motivated the extensive investigation into other metal complexes such as ruthenium. We herein present the synthesis and characterization of a new family of ruthenium compounds 1a–5a with the general formula [Ru(bipy)2L][CF3SO3]2 (bipy = 2,2′-bipyridine; L = bidentate ligand: N,N; N,P; P,P; P,As) which have been characterized by elemental analysis, ES-MS, 1H and 31P–{1H} NMR, FTIR and conductivity measurements. The molecular structures of four Ru(II) complexes were determined by single crystal X-ray diffraction. All compounds displayed moderate cytotoxic activity in vitro against human A2780 ovarian, MCF7 breast and HCT116 colorectal tumor cells. Compound 5a was the most cytotoxic compound against A2780 and MCF7 tumor cells with an IC50 of 4.75 ± 2.82 μM and 20.02 ± 1.46 μM, respectively. The compounds showed no cytotoxic effect on normal human primary fibroblasts but rather considerable selectivity for A2780, MCF7 and HCT116 tumor cells. All compounds induce apoptosis and autophagy in A2780 ovarian carcinoma cells and some nuclear DNA fragmentation. All compounds interact with CT-DNA with intrinsic binding constants in the order 1a > 4a > 2a > 3a > 5a. The observed hyperchromic effect may be due to the electrostatic interaction between positively charged cations and the negatively charged phosphate backbone at the periphery of the double helix-CT-DNA. Interestingly, compound 1a shows a concentration dependent DNA double strand cleavage. In addition in vivo toxicity has been evaluated on zebrafish embryos unveiling the differential toxicity between the compounds, with LC50 ranging from 8.67 mg L−1 for compound 1a to 170.30 mg L−1 for compound 2a.

Identification of novel molecules that can selectively inhibit the growth of tumor cells, avoid causing side effects to patients and/or intrinsic or acquired resistance, usually associated with common chemotherapeutic agents, is of utmost importance. Organometallic compounds have gained importance in oncologic chemotherapy, such as organotin(IV) complexes. In this study, we assessed the anti-tumor activity of the cyclic trinuclear organotin(IV) complex with an aromatic oximehydroxamic acid group [nBu(2)Sn(L)](3)(H2L = N,2-dihydroxy-5-[N-hydroxyethanimidoyl]benzamide) - MG85 - and provided further characterization of its biological targets. We have previously shown the high anti-proliferative activity of this complex against human colorectal and hepatocellular carcinoma cell lines and lower cytotoxicity in neonatal non-tumor fibroblasts. MG85 induces tumor cell apoptosis and down-regulation of proteins related to tubulin dynamics (TCTP and COF1). Further characterization included the: (i) evaluation of interference in the cell cycle progression, including the expression of critical genes; (ii) affinity to DNA and the corresponding mode of binding; (iii) genotoxic potential in cells with deficient DNA repair pathways; and (iv) in vivo tumor reduction efficiency using mouse colorectal carcinoma xenografts.

Reactions between 4'-phenyl-terpyridine (L) and several Cu(II) salts (p-toluenesulfonate, benzoate and o-, m-or p-hydroxybenzoate) led to the formation of [Cu(p-SO3C6H4CH3)L(H2O)(2)](p-SO3C6H4CH3) (1), [Cu(OCOPh)(2)L] (2), [Cu(o-OCOC6H4OH)(2)L] (3), [Cu(m-OCOC6H4OH)(2)L]center dot MeOH (4 center dot MeOH) and [Cu(pOCOC(6)H(4)OH)(2)L]center dot 2H(2)O (5 center dot 2H2O), which were characterized by elemental and TG-DTA analyses, ESI-MS, IR spectroscopy and single crystal X-ray diffraction, as well as by conductivimetry. In all structures the Cu atoms present N3O3 octahedral coordination geometries, which, in 2-5, are highly distorted as a result of the chelating-bidentate mode of one of the carboxylate ligands. Intermolecular pi...pi stacking interactions could also be found in 2-5 (in the 3.569-3.651 angstrom range and involving solely the pyridyl rings). Mediumstrong hydrogen bond interactions lead to infinite 1D chains (in 1 and 4) and to an infinite 2D network (in 5). Compounds 1 and 4 show high in vitro cytotoxicity towards HCT116 colorectal carcinoma and HepG2 hepatocellular carcinoma cell lines. The antiproliferative potential of compound 1 is due to an increase of the apoptotic process that was confirmed by Hoechst staining, flow cytometry and RT-qPCR. All compounds able to non-covalently intercalate the DNA helix and induce in vitro pDNA double-strand breaks in the absence of H2O2. Concerning compound 1, the hydroxyl radical and singlet oxygen do not appear to be involved in the pDNA cleavage process and the fact that this cleavage also occurs in the absence of molecular oxygen points to a hydrolytic mechanism of cleavage.

Several copper complexes have been assessed as anti-tumor agents against cancer cells. In this work, a copper compound [Cu(H2O){OS(CH3)(2)}L](NO3)(2) incorporating the ligand 4'-phenyl-terpyridine antiproliferative activity against human colorectal, hepatocellular carcinomas and breast adenocarcinoma cell lines was determined, demonstrating high cytotoxicity. The compound is able to induce apoptosis and a slight delay in cancer cell cycle progression, probably by its interaction with DNA and induction of double-strand pDNA cleavage, which is enhanced by oxidative mechanisms. Moreover, proteomic studies indicate that the compound induces alterations in proteins involved in cytoskeleton maintenance, cell cycle progression and apoptosis, corroborating its antiproliferative potential.

The majority of heterocycle compounds and typically common heterocycle fragments present in most pharmaceuticals currently marketed, alongside with their intrinsic versatility and unique physicochemical properties, have poised them as true cornerstones of medicinal chemistry. Apart from the already marketed drugs, there are many other being investigated for their promising activity against several malignancies. In particular, anticancer research has been capitalizing on the intrinsic versatility and dynamic core scaffold of these compounds. Nevertheless, as for any other promising anticancer drugs, heterocyclic compounds do not come without shortcomings. In this review, we provide for a concise overview of heterocyclic active compounds and families and their main applications in medicine. We shall focus on those suitable for cancer therapy while simultaneously addressing main biochemical modes of action, biological targets, structure-activity relationships as well as intrinsic limitation issues in the use of these compounds. Finally, considering the advent of nanotechnology for effective selective targeting of drugs, we shall discuss fundamental aspects and considerations on nanovectorization of such compounds that may improve pharmacokinetic/pharmacodynamic properties of heterocycles.

The therapeutic promise of small interfering RNAs (siRNAs) for specific gene silencing is dependent on the successful delivery of functional siRNAs to the cytoplasm. Their conjugation to an established delivery platform, such as gold nanoparticles, offers tremendous potential for treating diseases and advancing our understanding of cellular processes. Their success or failure is dependent on both the uptake of the nanoparticles into the cells and subsequent intracellular release of the functional siRNA. In this study, utilizing gold nanoparticle siRNA-mediated delivery against C-MYC, we aimed to determine if we could achieve knockdown in a cancer cell line with low levels of intracellular glutathione, and determine the influence, if any, of polyethylene glycol (PEG) ligand density on knockdown, with a view to determining the optimal nanoparticle design to achieve C-MYC knockdown. We demonstrate that, regardless of the PEG density, knockdown in cells with relatively low glutathione levels can be achieved, as well as the possible effect of steric hindrance of PEG on the availability of the siRNA for cleavage in the intracellular environment. Gold nanoparticle uptake was demonstrated via transmission electron microscopy and mass spectroscopy, while knockdown was determined at the protein and physiological levels (cells in S-phase) by in-cell westerns and BrdU incorporation, respectively.

Nanotheranostics takes advantage of nanotechnology-based systems in order to diagnose and treat a specific disease. This approach is particularly relevant for personalized medicine, allowing the detection of a disease at an early stage, to direct a suitable therapy toward the target tissue based on the molecular profile of the altered phenotype, subsequently facilitating disease monitoring and following treatment. A tailored strategy also enables to reduce the off-target effects associated with universal treatments and improve the safety profile of a given treatment. The unique optical properties of gold nanoparticles, their ease of surface modification, and high surface-to-volume ratio have made them central players in this area. By combining imaging, targeting, and therapeutic agents in a single vehicle, these nanoconjugates are (ought to be) an important tool in the clinics. In this review, the multifunctionality of gold nanoparticles as theranostics agents will be highlighted, as well as the requirements before the translation of these nanoplatforms into routine clinical practice.

The use of microfluidics platforms combined with the optimal optical properties of gold nanopartides has found plenty of application in molecular biosensing. This paper describes a biotnicrofluidic platform coupled to a non-cross-linking colorimetric gold nanoprobe assay to detect a single nucleotide polymorphism associated with increased risk of obesity fat-mass and obesity-associated (FTO) rs9939609 (Carlos et al., 2014). The system enabled significant discrimination between positive and negative assays using a target DNA concentration of 5 ng/mu l below the limit of detection of the conventionally used microplate reader (i.e., 15 ng/mu l) with 10 times lower solution volume (i.e., 3 mu l.). A set of optimization of our previously reported bio-microfluidic platform (Bemacka-Wojcik et al., 2013) resulted in a 160% improvement of colorimetric analysis results. Incorporation of planar microlenses increased 6 times signal-to-loss ratio reaching the output optical fiber improving by 34% the colorimetric analysis of gold nanopartides, while the implementation of an optoelectronic acquisition system yielded increased accuracy and reduced noise. The microfluidic chip was also integrated with a miniature fiber spectrometer to analyze the assays' cobrimetric changes and also the LEDs transmission spectra when illuminating through various solutions. Furthermore, by coupling an optical micmscope to a digital camera with a long exposure time (30s), we could visualise the different scatter intensities of gold nanoparticles within channels following salt addition. These intensities correlate well to the expected difference in aggregation between FTO positive (none to small aggregates) and negative samples (large aggregates). (C) 2015 Wiley Periodicals, Inc.

RNAi has always captivated scientists due to its tremendous power to modulate the phenotype of living organisms. This natural and powerful biological mechanism can now be harnessed to downregulate specific gene expression in diseased cells, opening up endless opportunities. Since most of the conventional siRNA delivery methods are limited by a narrow therapeutic index and significant side and off-target effects, we are now in the dawn of a new age in gene therapy driven by nanotechnology vehicles for RNAi therapeutics. Here, we outlook the {"}do's and dont's{"} of the inorganic RNAi nanomaterials developed in the last 15 years and the different strategies employed are compared and scrutinized, offering important suggestions for the next 15. (C) 2015 Elsevier Ltd. All rights reserved.