Inorganic nanoparticle-cored dendrimers for biomedical applications: A review.

Hybrid nanostructures exhibit a synergistic combination of features derived from their individual components, showcasing novel characteristics resulting from their distinctive structure and chemical/physical properties. Surface modifiers play a pivotal role in shaping INPs' primary attributes, influencing their physicochemical properties, stability, and functional applications. Among these modifiers, dendrimers have gained attention as highly effective multifunctional agents for INPs, owing to their unique structural qualities, dendritic effects, and physicochemical properties. Dendrimers can be seamlessly integrated with diverse inorganic nanostructures, including metal NPs, carbon nanostructures, silica NPs, and QDs. Two viable approaches to achieving this integration involve either growing or grafting dendrimers, resulting in inorganic nanostructure-cored dendrimers. The initial step involves functionalizing the nanostructures' surface, followed by the generation of dendrimers through stepwise growth or attachment of pre-synthesized dendrimer branches. This hybridization imparts superior qualities to the resulting structure, including biocompatibility, solubility, high cargo loading capacity, and substantial functionalization potential. Combining the unique properties of dendrimers with those of the inorganic nanostructure cores creates a multifunctional system suitable for diverse applications such as theranostics, bio-sensing, component isolation, chemotherapy, and cargo-carrying applications. This review summarizes the recent developments, with a specific focus on the last five years, within the realm of dendrimers. It delves into their role as modifiers of INPs and explores the potential applications of INP-cored dendrimers in the biomedical applications.

Optimal scheduling of the nanoparticle-mediated cancer photo-thermo-radiotherapy.

Maximal synergistic effect between photothermal therapy and radiotherapy (RT) may be achieved when the interval between these two modalities is optimal. In this study, we tried to determine the optimal schedule of the combined regime of RT and nano-photothermal therapy (NPTT), based on the cell cycle distribution and kinetics of cell death. To this end, alginate-coated iron oxide-gold core-shell nanoparticles (Fe3O4@Au/Alg NPs) were synthesized, characterized, and their photo-radio sensitization potency was evaluated on human nasopharyngeal cancer KB cells. Our results demonstrated that synthesized NPs have a good potential in radiotherapy and near-infrared (NIR) photothermal therapy. However, results from flow cytometry analysis indicated that a major portion of KB cells were accumulated in the most radiosensitive phases of cell cycle (G2/M) 24 h after NPTT. Moreover, the maximal synergistic anticancer efficacy (12.3% cell viability) was observed when RT was applied 24 h following the administration of NPTT (NPs [30 µg/mL, 4 h incubation time] + Laser [808 nm, 1 W/cm2, 5 min] + RT [6 Gy]). It is noteworthy that apoptosis was the dominant cell death pathway in the group of cells treated by combination of NPTT and RT. This highly synergistic anticancer efficacy provides a mechanistic basis for Fe3O4@Au/Alg NPs-mediated photothermal therapy combined with RT. Knowing such a basis is helpful to promote novel nanotechnology cancer treatment strategies.

Secondary toxic effect of graphene oxide and graphene quantum dots alters the expression of miR-21 and miR-29a in human cell lines.

For in vitro studies, non-toxic doses of nanomaterials are routinely selected by quantification of live cells after exposing to different concentrations of nanoparticles but considering only morphological changes or viability of cells is not sufficient to conclude that these nanomaterials are non-cytotoxic. Here we investigated if secondary toxicity is active in the cells exposed to non-toxic doses of graphene oxide (GO) and graphene quantum dots (GQDs). Non-cytotoxic dose of 15 µg mL-1 of GO (100 nm) and GQDs (50 nm) was selected according to MTT and Hoechst 33342/PI double staining assays. In order to investigate the secondary toxicity, the expression of miR-21, miR-29a and three genes at both mRNA and protein level were evaluated in MCF-7, HUVEC, KMBC/71 cells 4 and 24 h post exposure. Mitochondrial membrane potential (MMP) was assessed by Rhodamine 123 staining. According to our results, there was no significant decrease in viability of cells after exposure to the non-cytotoxic dose of GO and GQDs, but we observed significant alterations in the expression level of miR-21, miR-29a, Bax, Bcl2 and PTEN genes after treatment in all three cells. In addition to molecular changes, we observed alteration in mitochondrial activity at cellular level. However, we also observed that GO influenced the basal level of genes and MMP more compare to GQDs. Considering that all these genes are involved in breast tumor development and metastasis, the observed changes in miRNA expression and protein synthesis may alter cell fate and susceptibility and cause deviation in the desired outcome of GO and GQDs application in medical research.

Enhancement of chemoradiation by co-incorporation of gold nanoparticles and cisplatin into alginate hydrogel.

Nonspecificity and high toxicity limit the treatment efficacy and safety of chemoradiation therapy. Effective tumor targeting of anticancer drugs and radiosensitizing agents is highly desirable to amplify the efficacy of this standard cancer therapy approach. To achieve this goal, we exploited the synergy of cisplatin and gold nanoparticles (AuNPs) co-loaded into alginate hydrogel network, forming so-called ACA nanocomplex, and X-ray radiation. Cisplatin is a commonly used anticancer agent, and at the same time, along with AuNPs could function as radiosensitizers to enhance the radiation-induced damages through various pathways. The ACA nanocomplex improved the therapeutic efficiency of standard chemotherapy and yielded 79% growth inhibition in CT26 colon adenocarcinoma tumor after 28 days, which was significantly higher than that of 9% for free cisplatin administration. Moreover, the combination of ACA nanocomplex with 6 MV X-ray dramatically suppressed tumor growth up to 95%, showing 51% enhancement in antitumor activity compared to standard chemoradiation. The nanocomplex developed herein holds the promise to promote the efficiency of standard chemoradiation while maintaining the patient's safety through reducing the clinically administered doses of anticancer drug and X-ray. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B:2658-2663, 2019.

A novel metronidazole fluorescent nanosensor based on graphene quantum dots embedded silica molecularly imprinted polymer.

A novel optical nanosensor for detection of Metronidazole in biological samples was reported. Graphene quantum dots embedded silica molecular imprinted polymer (GQDs-embedded SMIP) was synthesized and used as a selective fluorescent probe for Metronidazole detection. The new synthesized GQDs-embedded SMIP showed strong fluorescent emission at 450nm excited at 365nm which quenched in presence of Metronidazole as a template molecule.. The quenching was proportional to the concentration of Metronidazole in a linear range of at least 0.2µM to 15µM. The limit of detection for metronidazole determination was obtained 0.15µM. The nanosensor successfully worked in plasma matrixes.

Cerium(III) Ion Sensing Based on Graphene Quantum Dots Fluorescent Turn-Off.

In this work, graphene quantum dots (GQDs) was synthesized through hydrothermal method and used as a photoluminescent bulk nano-chemosensor for detection of Ce3+ ion in the aqueous solution. The synthesized GQD was characterized by transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR), UV-Visible absorption and fluorescence emission spectroscopy. The sheet diameters of the synthesized GQDs were mainly distributed in the range of 15-20 nm. The interactions of GQDs with common cations and lanthanide ions were studied by fluorescence spectroscopy. Among the tested cations, Ce3+ ions was able to quench the fluorescence emission intensity of the GQD selectively. This quenching can be attributed to a redox mechanism between Ce3+ ion on the GQDs surface.

A novel solid-state electrochemiluminescence sensor for detection of cytochrome c based on ceria nanoparticles decorated with reduced graphene oxide nanocomposite.

A novel ultrasensitive sensing system for the rapid detection of cytochrome c (Cyt C) was developed on the basis of an electrochemiluminescence (ECL) method. A nanocomposite biosensor was made of reduced graphene oxide decorated with cerium oxide/tris(2,2-bipyridyl)ruthenium(II)/chitosan (CeO2NPs-RGO/ Ru(bpy)3 (2+)/CHIT) and used for this purpose. The ECL signal was produced by an electrochemical interaction between Ru(bpy)3 (2+) and tripropyl amine (TPA) on the surface of the electrode. Addition of Cyt C to the solution decreases the ECL signal due to its affinity for TPA and inhibition of its reaction with Ru(bpy)3 (2+). The effects of the amount of CeO2NPs-RGO, Ru(bpy)3 (2+), TPA concentration as a co-reactant, and the pH of the electrolyte solution on the ECL signal intensity were studied and optimized. The results showed that the method was fast, reproducible, sensitive, and stable for the detection of Cyt C. The method has a linear range from 2.5 nM to 2 µM (R (2) = 0.995) with a detection limit of 0.7 nM. Finally, the proposed biosensor was used for the determination of Cyt C in human serum samples with RSDs of 1.8-3.6 %. The results demonstrate that this solid-state ECL quenching biosensor has high sensitivity, selectivity, and good stability. Graphical Abstract A novel solid-state electrochemiluminescence sensor for detection of cytochrome C based on Ceria Nanoparticles Decorated Reduced Graphene Oxide Nanocomposite.

Detection of Aeromonas hydrophila DNA oligonucleotide sequence using a biosensor design based on Ceria nanoparticles decorated reduced graphene oxide and Fast Fourier transform square wave voltammetry.

A new strategy was introduced for ssDNA immobilization on a modified glassy carbon electrode. The electrode surface was modified using polyaniline and chemically reduced graphene oxide decorated cerium oxide nanoparticles (CeO2NPs-RGO). A single-stranded DNA (ssDNA) probe was immobilized on the modified electrode surface. Fast Fourier transform square wave voltammetry (FFT-SWV) was applied as detection technique and [Ru(bpy)3](2+/3+) redox signal was used as electrochemical marker. The hybridization of ssDNA with its complementary target caused a dramatic decrease in [Ru(bpy)3](2+/3+) FFT-SW signal. The proposed electrochemical biosensor was able to detect Aeromonas hydrophila DNA oligonucleotide sequence encoding aerolysin protein. Under optimal conditions, the biosensor showed excellent selectivity toward complementary sequence in comparison with noncomplementary and two-base mismatch sequences. The dynamic linear range of this electrochemical DNA biosensor for detecting 20-mer oligonucleotide sequence of A. hydrophila was from 1 × 10(-15) to 1 × 10(-8) mol L(-1). The proposed biosensor was successfully applied for the detection of DNA extracted from A. hydrophila in fish pond water up to 0.01 µg mL(-1) with RSD of 5%. Besides, molecular docking was applied to consider the [Ru(bpy)3](2+/3+) interaction with ssDNA before and after hybridization.

Facile sonochemical synthesis and electrochemical investigation of ceria/graphene nanocomposites.

The potential benefits of decorated graphene are of great interest as they may lead to technological advancements in fabricating electro-chemical devices for catalysis, sensing and energy storage. In this study, we have developed a self-assembly approach to anchor CeO2 nanoparticles on reduced graphene oxide (RGO) through a facile, efficient sonochemical method. We characterized the CeO2-RGO nanocomposites using X-ray diffraction (XRD), Fourier-transform infrared (FT-IR) spectroscopy, Raman spectroscopy and field-emission scanning electron microscopy (FE-SEM). The results reveal that CeO2 nanoparticles with a uniform size distribution are anchored on RGO. Furthermore, we investigated the electrochemical properties of CeO2-RGO nanocomposites for different probes by using cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) techniques. We found that a suitable loading content of CeO2 on RGO can induce a synergistic effect for optimizing the electro-catalytic activity of the nanocomposites. Our findings will have a profound effect on the use of CeO2-RGO nanocomposites in electrochemical devices.