Shahad Alsaiari

Protein-gold clusters-capped mesoporous silica nanoparticles for high drug loading, autonomous gemcitabine/doxorubicin co-delivery, and in-vivo tumor imaging.

Functional nanocarriers capable of transporting high drug contents without premature leakage and to controllably deliver several drugs are needed for better cancer treatments. To address this clinical need, gold cluster bovine serum albumin (AuNC@BSA) nanogates were engineered on mesoporous silica nanoparticles (MSN) for high drug loadings and co-delivery of two different anticancer drugs. The first drug, gemcitabine (GEM, 40wt%), was loaded in positively-charged ammonium-functionalized MSN (MSN-NH3(+)). The second drug, doxorubicin (DOX, 32wt%), was bound with negatively-charged AuNC@BSA electrostatically-attached onto MSN-NH3(+), affording highly loaded pH-responsive MSN-AuNC@BSA nanocarriers. The co-delivery of DOX and GEM was achieved for the first time via an inorganic nanocarrier, possessing a zero-premature leakage behavior as well as drug loading capacities seven times higher than polymersome NPs. Besides, unlike the majority of strategies used to cap the pores of MSN, AuNC@BSA nanogates are biotools and were applied for targeted red nuclear staining and in-vivo tumor imaging. The straightforward non-covalent combination of MSN and gold-protein cluster bioconjugates thus leads to a simple, yet multifunctional nanotheranostic for the next generation of cancer treatments.

Photoresponsive Bridged Silsesquioxane Nanoparticles with Tunable Morphology for Light-Triggered Plasmid DNA Delivery

Bridged silsesquioxane nanocomposites with tunable morphologies incorporating o-nitrophenylene-ammonium bridges are described. The systematic screening of the sol-gel parameters allowed the material to reach the nanoscale with controlled dense and hollow structures of 100-200 nm. The hybrid composition of silsesquioxanes with 50% organic content homogeneously distributed in the nanomaterials endowed them with photoresponsive properties. Light irradiation was performed to reverse the surface charge of nanoparticles from +46 to -39 mV via a photoreaction of the organic fragments within the particles, as confirmed by spectroscopic monitorings. Furthermore, such nanoparticles were applied for the first time for the on-demand delivery of plasmid DNA in HeLa cancer cells via light actuation.

Biodegradable Magnetic Silica@Iron Oxide Nanovectors with Ultra-Large Mesopores for High Protein Loading, Magnetothermal Release, and Delivery.

ABSTRACT The delivery of large cargos of diameter above 15 nm for biomedical applications has proved challenging since it requires biocompatible, stably‐loaded, and biodegradable nanomaterials. In this study, we describe the design of biodegradable silica‐iron oxide hybrid nanovectors with large mesopores for large protein delivery in cancer cells. The mesopores of the nanomaterials spanned from 20 to 60 nm in diameter and post‐functionalization allowed the electrostatic immobilization of large proteins (e.g. mTFP‐Ferritin, ˜534 kDa). Half of the content of the nanovectors was based with iron oxide nanophases which allowed the rapid biodegradation of the carrier in fetal bovine serum and a magnetic responsiveness. The nanovectors released large protein cargos in aqueous solution under acidic pH or magnetic stimuli. The delivery of large proteins was then autonomously achieved in cancer cells via the silica‐iron oxide nanovectors, which is thus a promising for biomedical applications. Graphical abstract Figure. No caption available.

Endosomal Escape and Delivery of CRISPR/Cas9 Genome Editing Machinery Enabled by Nanoscale Zeolitic Imidazolate Framework

CRISPR/Cas9 is a combined protein (Cas9) and an engineered single guide RNA (sgRNA) genome editing platform that offers revolutionary solutions to genetic diseases. It has, however, a double delivery problem owning to the large protein size and the highly charged RNA component. In this work, we report the first example of CRISPR/Cas9 encapsulated by nanoscale zeolitic imidazole frameworks (ZIFs) with a loading efficiency of 17% and enhanced endosomal escape promoted by the protonated imidazole moieties. The gene editing potential of CRISPR/Cas9 encapsulated by ZIF-8 (CC-ZIFs) is further verified by knocking down the gene expression of green fluorescent protein by 37% over 4 days. The nanoscale CC-ZIFs are biocompatible and easily scaled-up offering excellent loading capacity and controlled codelivery of intact Cas9 protein and sgRNA.

Engineering Hydrophobic Organosilica Nanoparticle-Doped Nanofibers for Enhanced and Fouling Resistant Membrane Distillation

Engineering and scaling-up new materials for better water desalination are imperative to find alternative fresh water sources to meet future demands. Herein, the fabrication of hydrophobic poly(ether imide) composite nanofiber membranes doped with novel ethylene-pentafluorophenylene-based periodic mesoporous organosilica nanoparticles is reported for enhanced and fouling resistant membrane distillation. Novel organosilica nanoparticles were homogeneously incorporated into electrospun nanofiber membranes depicting a proportional increase of hydrophobicity to the particle contents. Direct contact membrane distillation experiments on the organosilica-doped membrane with only 5% doping showed an increase of flux of 140% compared to commercial membranes. The high porosity of organosilica nanoparticles was further utilized to load the eugenol antimicrobial agent which produced a dramatic enhancement of the antibiofouling properties of the membrane of 70% after 24 h.

Supramolecular Self-Assembly of Histidine-Capped-Dialkoxy-Anthracene: A Visible Light Triggered Platform for facile siRNA Delivery

Supramolecular self-assembly of histidine-capped-dialkoxy-anthracene (HDA) results in the formation of light-responsive nanostructures. Single-crystal X-ray diffraction analysis of HDA shows two types of hydrogen bonding. The first hydrogen bond is established between the imidazole moieties while the second involves the oxygen atom of one amide group and the hydrogen atom of a second amide group. When protonated in acidic aqueous media, HDA successfully complexes siRNA yielding spherical nanostructures. This biocompatible platform controllably delivers siRNA with high efficacy upon visible-light irradiation leading up to 90 % of gene silencing in live cells.

Colloidal Gold Nanoclusters Spiked Silica Fillers in Mixed Matrix Coatings: Simultaneous Detection and Inhibition of Healthcare-Associated Infections

Healthcare-associated infections (HAIs) are the infections that patients get while receiving medical treatment in a medical facility with bacterial HAIs being the most common. Silver and gold nanoparticles (NPs) have been successfully employed as antibacterial motifs; however, NPs leaching in addition to poor dispersion and overall reproducibility are major hurdles to further product development. In this study, the authors design and fabricate a smart antibacterial mixed-matrix membrane coating comprising colloidal lysozyme-templated gold nanoclusters as nanofillers in poly(ethylene oxide)/poly(butylene terephthalate) amphiphilic polymer matrix. Mesoporous silica nanoparticles-lysozyme functionalized gold nanoclusters disperse homogenously within the polymer matrix with no phase separation and zero NPs leaching. This mixed-matrix coating can successfully sense and inhibit bacterial contamination via a controlled release mechanism that is only triggered by bacteria. The system is coated on a common radiographic dental imaging device (photostimulable phosphor plate) that is prone to oral bacteria contamination. Variation and eventually disappearance of the red fluorescence surface under UV light signals bacterial infection. Kanamycin, an antimicrobial agent, is controllably released to instantly inhibit bacterial growth. Interestingly, the quality of the images obtained with these coated surfaces is the same as uncoated surfaces and thus the safe application of such smart coatings can be expanded to include other medical devices without compromising their utility.

Tunable and Linker Free Nanogaps in Core–Shell Plasmonic Nanorods for Selective and Quantitative Detection of Circulating Tumor Cells by SERS

Controlling the size, number, and shape of nanogaps in plasmonic nanostructures is of significant importance for the development of novel quantum plasmonic devices and quantitative sensing techniques such as surface-enhanced Raman scattering (SERS). Here, we introduce a new synthetic method based on coordination interactions and galvanic replacement to prepare core-shell plasmonic nanorods with tunable enclosed nanogaps. Decorating Au nanorods with Raman reporters that strongly coordinate Ag+ ions (e.g., 4-mercaptopyridine) afforded uniform nucleation sites to form a sacrificial Ag shell. Galvanic replacement of the Ag shell by HAuCl4 resulted in Au-AgAu core-shell structure with a uniform intra-nanoparticle gap. The size (length and width) and morphology of the core-shell plasmonic nanorods as well as the nanogap size depend on the concentration of the coordination complexes formed between Ag+ ions and 4-mercaptopyridine. Moreover, encapsulating Raman reporters within the nanogaps afforded an internal standard for sensitive and quantitative SERS analysis. To test the applicability, core-shell plasmonic nanorods were functionalized with aptamers specific to circulating tumor cells such as MCF-7 (Michigan Cancer Foundation-7, breast cancer cell line). This system could selectively detect as low as 20 MCF-7 cells in a blood mimicking fluid employing SERS. The linking DNA duplex on core-shell plasmonic nanorods can also intercalate hydrophobic drug molecules such as Doxorubicin, thereby increasing the versatility of this sensing platform to include drug delivery. Our synthetic method offers the possibility of developing multifunctional SERS-active materials with a wide range of applications including biosensing, imaging, and therapy.

Microwave-Induced Chemotoxicity of Polydopamine-Coated Magnetic Nanocubes.

Polydopamine-coated FeCo nanocubes (PDFCs) were successfully synthesized and tested under microwave irradiation of 2.45 GHz frequency and 0.86 W/cm2 power. These particles were found to be non-toxic in the absence of irradiation, but gained significant toxicity upon irradiation. Interestingly, no increase in relative heating rate was observed when the PDFCs were irradiated in solution, eliminating nanoparticle (NP)-induced thermal ablation as the source of toxicity. Based on these studies, we propose that microwave-induced redox processes generate the observed toxicity.