Basem A. Moosa

Electrostatic Assembly/Disassembly of Nanoscaled Colloidosomes for Light‐Triggered Cargo Release

Colloidosome capsules possess the potential for the encapsulation and release of molecular and macromolecular cargos. However, the stabilization of the colloidosome shell usually requires an additional covalent crosslinking which irreversibly seals the capsules, and greatly limits their applications in large-cargos release. Herein we report nanoscaled colloidosomes designed by the electrostatic assembly of organosilica nanoparticles (NPs) with oppositely charged surfaces (rather than covalent bonds), arising from different contents of a bridged nitrophenylene-alkoxysilane [NB; 3-nitro-N-(3-(triethoxysilyl)propyl)-4-(((3-(triethoxysilyl)propyl)-amino)methyl)benzamid] derivative in the silica. The surface charge of the positively charged NPs was reversed by light irradiation because of a photoreaction in the NB moieties, which impacted the electrostatic interactions between NPs and disassembled the colloidosome nanosystems. This design was successfully applied for the encapsulation and light-triggered release of cargos.

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.

Cytotoxicity and Apoptosis Induced by a Plumbagin Derivative in Estrogen Positive MCF-7 Breast Cancer Cells

Plumbagin [5-hydroxy- 2-methyl-1, 4-naphthaquinone] is a well-known plant derived anticancer lead compound. Several efforts have been made to synthesize its analogs and derivatives in order to increase its anticancer potential. In the present study, plumbagin and its five derivatives have been evaluated for their antiproliferative potential in one normal and four human cancer cell lines. Treatment with derivatives resulted in dose- and time-dependent inhibition of growth of various cancer cell lines. Prescreening of compounds led us to focus our further investigations on acetyl plumbagin, which showed remarkably low toxicity towards normal BJ cells and HepG2 cells. The mechanisms of apoptosis induction were determined by APOPercentage staining, caspase-3/7 activation, reactive oxygen species production and cell cycle analysis. The modulation of apoptotic genes (p53, Mdm2, NF-kB, Bad, Bax, Bcl-2 and Casp-7) was also measured using real time PCR. The positive staining using APOPercentage dye, increased caspase-3/7 activity, increased ROS production and enhanced mRNA expression of proapoptotic genes suggested that acetyl plumbagin exhibits anticancer effects on MCF-7 cells through its apoptosis-inducing property. A key highlighting point of the study is low toxicity of acetyl plumbagin towards normal BJ cells and negligible hepatotoxicity (data based on HepG2 cell line). Overall results showed that acetyl plumbagin with reduced toxicity might have the potential to be a new lead molecule for testing against estrogen positive breast cancer.

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.

Experimental and theoretical evaluation of nanodiamonds as pH triggered drug carriers

Nanodiamond (ND) and its derivatives have been widely used for drug, protein and gene delivery. Herein, experimental and theoretical methods have been combined to investigate the effect of pH on the delivery of doxorubicin (DOX) from fluorescein labeled NDs (Fc-NDs). In the endosomal recycling process, the nanoparticle will pass from mildly acidic vesicle to pH ≈ 4.8; thus, it is important to investigate DOX release from NDs at different pH values. Fc-NDs released DOX dramatically under acidic conditions, while an increase in the DOX loading efficiency (up to 6.4 wt%) was observed under basic conditions. Further theoretical calculations suggest that H+ weakens the electrostatistic interaction between ND surface carboxyl groups and DOX amino groups, and the interaction energies at pH 7 are 10.4 kcal mol−1, 25.0 kcal mol−1 and 27.0 kcal mol−1 respectively. Cellular imaging experiments show that Fc-NDs are readily ingested by breast adenocarcinoma (BA) cells and cell viability tests prove that they can be utilized as a safe drug delivery vehicle. Furthermore, pH triggered DOX release has been tested in vitro (pH 7.4 and pH 4.83) in breast adenocarcinoma (BA) cells.

pH-triggered micellar membrane for controlled release microchips

A pH-responsive membrane based on polystyrene-b-poly(4-vinylpyridine) (PS-b-P4VP) block copolymer was developed on a model glass microchip as a promising controlled polymer delivery system. The PS-b-P4VP copolymer assembles into spherical and/or worm-like micelles with styrene block cores and pyridine coronas in selective solvents. The self-assembled worm-like morphology exhibited pH-responsive behaviour due to the protonation of the P4VP block at low pH and its deprotonation at high pH and thus constituting a switchable “off/on” system. Doxorubicin (Dox) was used as cargo to test the PS-b-P4VP membrane. Luminescence experiments indicated that the membrane was able to store Dox molecules within its micellar structure at neutral pH and then release them as soon as the pH was raised to 8.0. The performance of the cast membrane was predictable and most importantly reproducible. The physiochemical and biological properties were also investigated carefully in terms of morphology, cell viability and cell uptake.

Fullerene‐Catalyzed Reduction of Azo Derivatives in Water under UV Irradiation

Metal-free fullerene (C(60)) was found to be an effective catalyst for the reduction of azo groups in basic aqueous solution under UV irradiation in the presence of NaBH(4). Use of NaBH(4) by itself is not sufficient to reduce the azo dyes without the assistance of a metal catalyst such as Pd and Ag. Experimental and theoretical results suggest that C(60) catalyzes this reaction by using its vacant orbital to accept the electron in the bonding orbital of azo dyes, which leads to the activation of the N=N bond. UV irradiation increases the ability of C(60) to interact with electron-donor moieties in azo dyes.

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.

Degradable gold core–mesoporous organosilica shell nanoparticles for two-photon imaging and gemcitabine monophosphate delivery

The synthesis of degradable gold core–mesoporous organosilica shell nanoparticles is described. The nanoparticles were very efficient for two-photon luminescence imaging of cancer cells and for in vitro gemcitabine monophosphate delivery, allowing promising theranostic applications in the nanomedicine field.

Anisotropic Self-Assembly of Organic–Inorganic Hybrid Microtoroids

Toroidal structures based on self-assembly of predesigned building blocks are well-established in the literature, but spontaneous self-organization to prepare such structures has not been reported to date. Here, organic-inorganic hybrid microtoroids synthesized by simultaneous coordination-driven assembly of amphiphilic molecules and hydrophilic polymers are reported. Mixing amphiphilic molecules with iron(III) chloride and hydrophilic polymers in water leads, within minutes, to the formation of starlike nanostructures. A spontaneous self-organization of these nanostructures is then triggered to form stable hybrid microtoroids. Interestingly, the toroids exhibit anisotropic hierarchical growth, giving rise to a layered toroidal framework. These microstructures are mechanically robust and can act as templates to host metallic nanoparticles such as gold and silver. Understanding the nature of spontaneous assembly driven by coordination multiple non-covalent interactions can help explain the well-ordered complexity of many biological organisms in addition to expanding the available tools to mimic such structures at a molecular level.