Designing of a Multifunctional 3D-Printed Biomimetic Theragenerative Aerogel Scaffold via Mussel-Inspired Chemistry: Bioactive Glass Nanofiber-Incorporated Self-Assembled Silk Fibroin with Antibacterial, Antiosteosarcoma, and Osteoinductive Properties.

Biomaterial-mediated bone tissue engineering (BTE) offers an alternative, interesting approach for the restoration of damaged bone tissues in postsurgery osteosarcoma treatment. This study focused on synthesizing innovative composite inks, integrating self-assembled silk fibroin (SF), tannic acids (TA), and electrospun bioactive glass nanofibers 70SiO2-25CaO-5P2O5 (BGNF). By synergistically combining the unique characteristics of these three components through self-assembly and microextrusion-based three-dimensional (3D) printing, our goal was to produce durable and versatile aerogel-based 3D composite scaffolds. These scaffolds were designed to exhibit hierarchical porosity along with antibacterial, antiosteosarcoma, and bone regeneration properties. Taking inspiration from mussel foot protein attachment chemistry involving the coordination of dihydroxyphenylalanine (DOPA) amino acids with ferric ions (Fe3+), we synthesized a tris-complex catecholate-iron self-assembled composite gel. This gel formation occurred through the coordination of oxidized SF (SFO) with TA and polydopamine-modified BGNF (BGNF-PDA). The dynamic nature of the coordination ligand-metal bonds within the self-assembled SFO matrix provided excellent shear-thinning properties, allowing the SFO-TA-BGNF complex gel to be extruded through a nozzle, facilitating 3D printing into scaffolds with outstanding shape fidelity. Moreover, the developed composite aerogels exhibited multifaceted features, including NIR-triggered photothermal antibacterial and in vitro photothermal antiosteosarcoma properties. In vitro studies showcased their excellent biocompatibility and osteogenic features as seeded cells successfully differentiated into osteoblasts, promoting bone regeneration in 21 days. Through comprehensive characterizations and biological validations, our antibacterial scaffold demonstrated promise as an exceptional platform for concurrent bone regeneration and bone cancer therapy, setting the stage for their potential clinical application.

MXene-Integrated Silk Fibroin-Based Self-Assembly-Driven 3D-Printed Theragenerative Scaffolds for Remotely Photothermal Anti-Osteosarcoma Ablation and Bone Regeneration.

Aiming to address the bone regeneration and cancer therapy functionalities in one single material, in this study, we developed a dual-functional theragenerative three-dimensional (3D) aerogel-based composite scaffold from hybridization of photo-cross-linked silk fibroin (SF) biopolymer with MXene (Ti3C2) two-dimensional (2D) nanosheets. To fabricate the scaffold, we first develop a dual-cross-linked SF-based aerogel scaffold through 3D printing and photo-cross-linking of the self-assembly-driven methacrylate-modified SF (SF-MA) gel with controlled pore size, macroscopic geometry, and mechanical stability. In the next step, to endow a remotely controlled photothermal antiosteosarcoma ablation function to fabricated aerogel scaffold, MXene 2D nanosheets with strong near-infrared (NIR) photon absorption properties were integrated into the 3D-printed scaffolds. While 3D-printed MXene-modified dual-cross-linked SF composite scaffolds can mediate the in vitro growth and proliferation of preosteoblastic cell lines, they also endow a strong photothermal effect upon remote irradiation with NIR laser but also significantly stimulate bone mineral deposition on the scaffold surface. Additionally, besides the local release of the anticancer model drug, the generated heat (45-53 °C) mediated the photothermal ablation of cancer cells. The developed aerogel-based composites and chosen therapeutic techniques are thought to render a significant breakthrough in biomaterials' future clinical applications.

Validation of Dual-Action Chemo-Radio-Labeled Nanocarriers with High Efficacy against Triple-Negative Breast Cancer.

Identification and selectivity of molecular targets with prolonged action for difficult-to-target cancer such as triple-negative breast cancer (TNBC) represent a persisting challenge in the precision delivery of therapeutics. In the quest to target undruggable sites, this study validates the bioavailability of polydopamine-sealed mesoporous silica nanocarriers (PDA-mSiO2) for in vivo drug delivery to TNBC. For controlled transport and release, the chemotherapeutic drug doxorubicin was encapsulated in mSiO2 nanocarriers coated with a PDA layer serving as a stimuli-responsive gatekeeper or seal. For unifying targeting and treatment modalities, these nanocarriers were covalently conjugated to a macrocyclic chelator (DOTA) and folate (FA-mSiO2.) that enabled incorporation of radionuclides and identification of FR Alpha (FolRα) receptors present on TNBC cells. The robust chemical design of FA- and DOTA-functionalized PDA-coated mSiO2 nanocarriers constitutes mild reaction conditions to avoid the loss of surface-bound molecules. The radiolabeling studies with the theranostic pair 68Ga and 177Lu showed quantitative trends for radiochemical efficacy and purity. Nanocarriers equipped with both radiolabels and affinity ligands were optimally stable when incubated with human serum for up to 120 h (177Lu), demonstrating hydrophilicity with a partition coefficient (log P) of -3.29 ± 0.08. Specifically, when incubated with TNBC cells, the cells received significant FA-mSiO2 carriers, demonstrating efficient carrier internalization and time-dependent uptake. Moreover, in vivo results visualize the retention of drug-filled carriers at the tumor sites for a long time, which holds promise for therapeutic studies. This research work demonstrates for the first time the successful dual conjugation of nanocarriers through the colocation of radionuclides and anticancer drugs that is promising for both live molecular imaging and enhanced therapeutic effect for TNBC.

Fabrication and Characterization of Piezoelectric Polymer Composites and Cytocompatibility with Mesenchymal Stem Cells.

Piezoelectric materials are promising for biomedical applications because they can provide mechanical or electrical stimulations via converse or direct piezoelectric effects. The stimulations have been proven to be beneficial for cell proliferation and tissue regeneration. Recent reports showed that doping different contents of reduced graphene oxide (rGO) or polyaniline (PANi) into biodegradable polyhydroxybutyrate (PHB) enhanced their piezoelectric response, showing potential for biomedical applications. In this study, we aim to determine the correlation between physiochemical properties and the in vitro cell response to the PHB-based composite scaffolds with rGO or PANi. Specifically, we characterized the surface morphology, wetting behavior, electrochemical impedance, and piezoelectric properties of the composites and controls. The addition of rGO and PANi resulted in decreased fiber diameters and hydrophobicity of PHB. The increased surface energy of PHB after doping nanofillers led to a reduced water contact angle (WCA) from 101.84 ± 2.18° (for PHB) to 88.43 ± 0.83° after the addition of 3 wt % PANi, whereas doping 1 wt % rGO decreased the WCA value to 92.56 ± 2.43°. Meanwhile, doping 0.2 wt % rGO into PHB improved the piezoelectric properties compared to the PHB control and other composites. Adding up to 1 wt % rGO or 3 wt % PANi nanofillers in PHB did not affect the adhesion densities of bone marrow-derived mesenchymal stem cells (BMSCs) on the scaffolds. The aspect ratios of attached BMSCs on the composite scaffolds increased compared to the PHB control. The study indicated that the PHB-based composites are promising for potential applications such as regenerative medicine, tissue stimulation, and bio-sensing, which should be further studied.

Rational design of bifunctional chimeric peptides that combine antimicrobial and titanium binding activity.

Bacterial biofilm formation remains a serious problem for clinical materials and often leads to implant failure. To counteract bacterial adhesion, which initiates biofilm formation, the development of antibiotic surface coating strategies is of high demand and warrants further investigations. In this study, we have created bifunctional chimeric peptides by fusing the recently developed antimicrobial peptide MGD2 (GLRKRLRKFFNKIKF) with different titanium-binding sequences. The novel peptides were investigated regarding their antibacterial potential against a set of different bacterial strains including drug-resistant Staphylococcus aureus. All peptides showed high antimicrobial activities both when in solution and when immobilized on titanium surfaces. Owing to the ease of synthesis and handling, the herein described peptides might be a true alternative to prevent bacterial biofilm formation.

Correction: Click functionalized biocompatible gadolinium oxide core-shell nanocarriers for imaging of breast cancer cells.

[This corrects the article DOI: 10.1039/D2RA00347C.].

Click functionalized biocompatible gadolinium oxide core-shell nanocarriers for imaging of breast cancer cells.

Site-specific delivery using functionalized nanocarriers is in high demand in imaging applications of modern clinical research. To improve the imaging capabilities of conventionally used contrast agents and expand the targeting accuracy, functional gadolinium oxide based nanocarriers originated from homogeneous core shells structures (Gd2O3@SiO2@Fe3O4) were developed using a multilayer formation approach. The synthesis and chemical configuration for the covalent binding of macrocyclic chelating agents and estrogen targeting molecules on these nanocarriers were designed by a two-step chemical synthesis method. Initially, SiO2@Fe3O4 structures were prepared and encapsulated with a homogenous thin Gd2O3 overlayer. The exterior surface of the as-prepared carriers offered chemical binding with a breast cancer specific estrogen molecule, covalently grafted through a Click-Chemistry protocol. In the next step, to enhance the diagnostic imaging capabilities of these carriers, thiocyanate-linked chelator molecule, DOTA, was attached to the surface of estrogen bound Gd2O3@SiO2@Fe3O4 using basic reaction conditions. The active amino groups before and after conjugation of estrogen molecules on the surface were quantified using a fluorescamine based approach. Due to the covalent binding of the macrocyclic chelator to the Gd2O3@SiO2@Fe3O4 surface, core shell carriers showed potential radiolabeling efficiency using positron emitter radionuclide, gallium-68 (68Ga). Intracellular uptake of estrogen-conjugated carriers was evaluated with MCF7 breast cancer cell lines using confocal laser scanning microscopy and fluorescent flow cytometry. In addition, in vitro cytotoxicity studies of functional nanocarriers as compared to bare nanoparticles showed reduced toxicity to HEK-293 cells demonstrating the role of surface attached molecules in preventing direct exposure of the Gd2O3 surface to the cells. The as-developed gadolinium based nanocarriers presented excellent capabilities as biocompatible target-specific imaging probes which indicates great potential in the field of dual-mode contrast agents.

Self-supported amorphous TaNx(Oy)/nickel foam thin film as an advanced electrocatalyst for hydrogen evolution reaction.

Chemical vapor deposited (CVD) amorphous tantalum-oxy nitride film on porous three-dimensional (3D) nickel foam (TaNx(Oy)/NF) utilizing tantalum precursor, tris(diethylamino)(ethylimino)tantalum(V), ([Ta(NEt)(NEt2)3]) with preformed Ta-N bonds is reported as a potential self-supported electrocatalyst for hydrogen evolution reaction (HER). The morphological analyses revealed the formation of thin film of core-shell structured TaNx(Oy) coating (ca. 236 nm) on NF. In 0.5 M H2SO4, TaNx(Oy)/NF exhibited enhanced HER activity with a low onset potential as compared to the bare NF (-50 mV vs. -166 mV). The TaNx(Oy)/NF samples also displayed higher current density (-11.08 mA cm-2vs. -3.36 mA cm-2 at 400 mV), lower Tafel slope (151 mV dec-1vs. 179 mV dec-1) and lower charge transfer resistance exemplifying the advantage of TaNx(Oy) coating towards enhanced HER performance. The enhanced HER catalytic activity is attributed to the synergistic effect between the amorphous TaNx(Oy) film and the nickel foam.

High efficiency capture of biomarker miRNA15a for noninvasive diagnosis of malignant kidney tumors.

To date, there are no preoperative and quantitative dynamics in clinical practice that can reliably differentiate between a benign and malignant renal cell carcinoma (RCC). For monitoring different analytes in body fluids, more than 40 different molecular biomarkers have been identified, however, they are associated with limited clinical sensitivity and/or non-optimal specificity due to their leaky nature. Previous work on RCC demonstrated the miRNA15a to be reliable and novel biomarker with 98.1% specificity and 100% sensitivity. Despite the high potential of miRNA15a biomarker, its clinical application is considerably hampered by the insensitive nature of the detection methods and low concentration of biomarker in samples that is aggravated by the high level of contamination due to other solutes present in body fluids. In this work, a non-invasive quantitative approach is demonstrated to overcome such diagnostics issues through biotin-streptavidin binding and fluorescence active magnetic nanocarriers that ensured prompt isolation, enrichment and purification of the biomarker miRNA15a from urine. The study demonstrates that detectable low levels of these miRNAs through miRNA capturing nanocarriers can potentially function as advanced diagnostic markers for the non-invasive investigation and early detection of renal cancer.

Synthesis, proteolytic stability, and in vitro evaluation of DOTA conjugated p160 peptide based radioconjugates: [177Lu]Lu-DOTA-p160.

In this work, we describe the synthesis, in vitro stability, and preliminary biological evaluation of [177Lu]Lu-DOTA-p160 peptide-based radiopharmaceuticals. Our findings highlight that all DOTA-p160-peptide radioconjugates exhibit favorable proteolytic and enzymatic stability with a prolonged half-life in human plasma and serum. Cell uptake studies carried out on MCF-7 cell line revealed saturable binding of the radioconjugates in the nanomolar range, thereby demonstrating their promising potential in the imaging and therapy of breast tumors.

18F-Labeled magnetic nanovectors for bimodal cellular imaging.

Surface modification of nanocarriers enables selective attachment to specific molecular targets within a complex biological environment. Besides the enhanced uptake due to specific interactions, the surface ligands can be utilized for radiolabeling applications for bimodal imaging ensured by positron emission topography (PET) and magnetic resonance imaging (MRI) functions in one source. Herein, we describe the surface functionalization of magnetite (Fe3O4) with folic acid as a target vector. Additionally, the magnetic nanocarriers were conjugated with appropriate ligands for subsequent copper-catalyzed azide-alkyne cycloaddition or carbodiimide coupling reactions to successfully achieve radiolabeling with the PET-emitter 18F. The phase composition (XRD) and size analysis (TEM) confirmed the formation of Fe3O4 nanoparticles (6.82 nm ± 0.52 nm). The quantification of various surface functionalities was performed by Fourier-transform infrared spectroscopy (FT-IR) and ultraviolet-visible microscopy (UV-Vis). An innovative magnetic-HPLC method was developed in this work for the determination of the radiochemical yield of the 18F-labeled NPs. The as-prepared Fe3O4 particles demonstrated high radiochemical yields and showed high cellular uptake in a folate receptor overexpressing MCF-7 cell line, validating bimodal imaging chemical design and a magnetic HPLC system. This novel approach, combining folic acid-capped Fe3O4 nanocarriers as a targeting vector with 18F labeling, is promising to apply this probe for bimodal PET/MR-studies.

Receptor-Mediated In Vivo Targeting of Breast Cancer Cells with 17α-Ethynylestradiol-Conjugated Silica-Coated Gold Nanoparticles.

Efficient therapies for breast cancer remain elusive because of the lack of strategies for targeted transport and receptor-mediated uptake of synthetic drug molecules by cancer cells. Conjugation of nanoparticles (NPs) with active targeting ligands enabling selective molecular recognition of antigens expressed on the surface of cancer cells is promising for localization and treatment of malignant cells. In this study, covalent attachment of synthetic estrogen 17α-ethynylestradiol on the silica (SiO2) shell of silica-gold NPs (SiO2@Au) was undertaken to improve the cancer-targeting ability of the nano-biotags. Chemical and structural analysis of the bioconjugates examined in solution (UV-vis and ξ-potential) and solid state (Fourier transform infrared spectroscopy, X-ray diffractometry, and transmission electron microscopy) confirmed the identity of the carrier particles and surface-bound ligands. The mesoporous silica shell served as a reservoir for anticancer drugs (doxorubicin and quercetin) and to facilitate covalent attachment of receptor molecules by click chemistry protocols. The chemoselective recognition between the nanoconjugates and cell membranes was successfully demonstrated by the accumulation of nanoprobes in the tumor tissue of mice with subcutaneous breast cancer, whereas healthy cells were unaffected. The drug release studies showed sustained release kinetics over several weeks. These findings elaborate the exceptional selectivity and potential of estrogen-coated nano-biolabels in efficient diagnosis and detection of breast cancer cells.

Synthesis of nickel-copper composite with controllable nanostructure through facile solvent control as positive electrode for high-performance supercapacitors.

The surface characteristics of electrodes vary depending on the solvent used. Furthermore, electrochemical performance varies depending on the surface morphology of the electrode. In this study, we grew 3D binary NiCu-based composites on Ni foam, via a binder-free hydrothermal method, for use as a cathode in high-performance supercapacitors. We employed different solvents to prepare the electrodes by adjusting the ratio of deionized water (DI water) to methanol. The electrode prepared using DI water as the solvent had the largest surface area with a nanowire structure. This morphology allowed for good electrical performance by greatly improving the electrode and electrolyte contact area and shortening the ion diffusion path. The optimized deposition of NiCu(CO3)(OH)2 nanowires (50 mL of DI water as solvent) showed an excellent maximum specific capacity of 758.9 mA h g-1 at a current density of 3 A g-1, as well as outstanding cycling performance with 87.2% retention after 5000 cycles. In this work, we focused on the large specific surface area and suitable electrochemical properties of NiCu(CO3)(OH)2 electrodes with various solvents. As a result, the asymmetric supercapacitor (ASC) using the NiCu(CO3)(OH)2 electrode prepared with 50 ml of DI water as the solvent as the positive electrode and graphene as the negative electrode, exhibited an energy density of 26.7 W h kg-1 at a power density of 2534 W kg-1, and excellent cycling stability with 91.3% retention after 5000 cycles. The NiCu(CO3)(OH)2//graphene ASC could turn on an LED light and demonstrated better electrical performance than most previously reported nickel- and copper-based carbonate hydroxide ASCs. In addition, in the present scenario where many nanoscale studies are conducted, a method of controlling the nanostructure of a material through facile solvent control will be of great help to many researchers.

Gelation of uranyl ions and gel-derived uranium oxide nanoparticles for gas sensing.

We developed a sol-gel method to synthesize uranium oxide nanoparticles with a clean surface and mixed valences of uranium at the surface. Uranyl gel was formed in ethylene glycol without incorporating any organic gelator and was readily converted to uranium dioxide nanoparticles with uniform size via microwave treatment. The as-prepared uranyl gel showed a high storage modulus of 0.48 kPa. The formation of the gel skeleton benefits from interlinkage of uranyl ions, which was revealed by UV-Vis spectroscopy and X-ray absorption. The U[double bond, length as m-dash]Oax bond was elongated by 0.1 Šand the U-Oeq bond was shortened by 0.25 Šby the gelation. The gel showed thixotropic and self-healing properties owing to the soft connection in the gel skeleton and photo-response attributed to the photo-reduction reaction between uranyl ions and matrix solvent. With the great inclusion properties, the uranyl gel was decomposed by microwave treatment into uranium dioxide nanoparticles with a size of ∼4 nm. The resultant UO2 nanoparticles were easily oxidized in air, and thus presented an n-type semiconductor behaviour and sensitivity to both oxidative and reductive gases such as NO2, EtOH, CO, and NH3.

Mediating the Fate of Cancer Cell Uptake: Dual-Targeted Magnetic Nanovectors with Biotin and Folate Surface Ligands.

Recognition of folate and biotin surface receptors by dual-functionalized nanoparticles (NPs) is key for site-selective receptor-mediated transport of anticancer drugs to cancer cells. We present here dopamine-capped iron oxide nanoprobes (Fe3O4, 10 ± 2 nm) containing two surface-grafted biologically relevant ligands, namely, folic acid (FA) and biotin (BT). The covalent attachment of both FA and BT on Fe3O4 nanoparticles was achieved by following carbodiimide coupling and click-chemistry protocols. The dual-function Fe3O4 probes were delivered into E-G7 and human HeLa cancer cell lines and tested toward their cellular uptake by immunofluorescence and flow cytometry analysis. Owing to receptor-mediated endocytosis, enhanced accumulation of nanoprobes in cancer cells was successfully monitored by confocal laser microscopy. When compared to dual-function probes, single-functionalized nanoparticles possessing either FA or BT ligands showed significantly reduced uptake in the tested cell lines, underlining the superior interaction potential of dual-purpose probes. A time-dependent receptor-mediated endocytosis of FA-Fe3O4-BT nanovectors was demonstrated by flow cytometry analysis, whereas the unfunctionalized NPs did not show any specificity in terms of uptake. Besides their specific uptake, the surface-functionalized nanoparticles exhibited promising cytotoxicity profiles by demonstrating good viability of more than 95% with analogous cancer cell lines. Our results demonstrate that dual and/or multivariate conjugation of receptor-specific ligands on NPs is highly effective in molecular recognition of surface biomarkers that enhances their potential in anticancer treatment for pretargeting-radio strategies based on biotin/avidin interactions.

Magnetic Field-Assisted Chemical Vapor Deposition of Iron Oxide Thin Films: Influence of Field-Matter Interactions on Phase Composition and Morphology.

Magnetic field-assisted CVD offers a direct pathway to manipulate the evolution of microstructure, phase composition, and magnetic properties of the as-prepared film. We report on the role of applied magnetic fields (0.5 T) during a cold-wall CVD deposition of iron oxide from [FeIII(OtBu)3]2 leading to higher crystallinity, larger particulates, and better out-of-plane magnetic anisotropy, if compared with zero-field depositions. Whereas selective formation of homogeneous magnetite films was observed for the field-assisted process, coexistence of hematite and amorphous iron(III) oxide was confirmed under zero-field conditions. Comparison of the coercive field (11 vs 60 mT) indicated lower defect concentration for the field-assisted process with nearly superparamagnetic behavior. X-ray photoemission electron microscopy (X-PEEM) in absorption mode at the O-K and Fe-L3,2 edges confirmed the selective formation of magnetite (field-assisted) and hematite (zero-field) with coexisting amorphous phases, respectively, emphasizing the importance of field-matter interactions in the phase-selective synthesis of magnetic thin films.

Mechanically Strong Silica-Silk Fibroin Bioaerogel: A Hybrid Scaffold with Ordered Honeycomb Micromorphology and Multiscale Porosity for Bone Regeneration.

Due to the synergic feature of individual components in hybrid (nano)biomaterials, their application in regenerative medicine has drawn significant attention. Aiming to address all the current challenges of aerogel as a potent scaffold in bone tissue engineering application, we adopted a novel synthesis approach to synergistically improve the pore size regime and mechanical strength in the aerogel. The three-dimensional aerogel scaffold in this study has been synthesized through a versatile one-pot aqueous-based sol-gel hybridization/assembly of organosilane (tetraethyl orthosilicate) and silk fibroin (SF) biopolymer, followed by unidirectional freeze-casting of the as-prepared hybrid gel and supercritical drying. The developed ultralight silica-SF aerogel hybrids demonstrated a hierarchically organized porous structure with interesting honeycomb-shaped micromorphology and microstructural alignment (anisotropy) in varied length scales. The average macropore size of the hybrid aerogel lied in ∼0.5-18 µm and was systematically controlled with freeze-casting conditions. Together with high porosity (91-94%), high Young's modulus (∼4-7 MPa, >3 order of magnitude improvement compared to their pristine aerogel counterparts), and bone-type anisotropy in the mechanical compressive behavior, the silica-SF hybrid aerogel of this study acted as a very competent scaffold for bone tissue formation. The results of in vitro assessments revealed that the silica-SF aerogel is not only cytocompatible and nonhemolytic but also acted as an open porous microenvironment to trigger osteoblast cell attachment, growth, and proliferation on its surface within 14 days of incubation. Moreover, to support the in vitro results, in vivo bone formation within the aerogel implant in the bone defect site was studied. The X-ray radiology and microcomputed tomography analyses confirmed that a significant new bone tissue density formed in the defect site within 25 days of implantation. Also, in vivo toxicology studies showed a zero-toxic impact of the aerogel implant on the blood biochemical and hematological parameters. Finally, the study clearly shows the potential of aerogel as a bioactive and osteoconductive open porous cellular matrix for a successful osseointegration process.

Selective Capture and Purification of MicroRNAs and Intracellular Proteins through Antisense-vectorized Magnetic Nanobeads.

MicroRNAs (miRNAs) are small non-coding nucleotides playing a crucial role in posttranscriptional expression and regulation of target genes in nearly all kinds of cells. In this study, we demonstrate a reliable and efficient capture and purification of miRNAs and intracellular proteins using magnetic nanoparticles functionalized with antisense oligonucleotides. For this purpose, a tumor suppressor miRNA (miR-198), deregulated in several human cancer types, was chosen as the model oligonucleotide. Magnetite nanoparticles carrying the complementary sequence of miR-198 (miR-198 antisense) on their surface were delivered into cells and subsequently used for the extracellular transport of miRNA and proteins. The successful capture of miR-198 was demonstrated by isolating RNA from magnetic nanoparticles followed by real-time PCR quantification. Our experimental data showed that antisense-coated particles captured 5-fold higher amounts of miR-198 when compared to the control nanoparticles. Moreover, several proteins that could play a significant role in miR-198 biogenesis were found attached to miR-198 conjugated nanoparticles and analyzed by mass spectrometry. Our findings demonstrate that a purpose-driven vectorization of magnetic nanobeads with target-specific recognition ligands is highly efficient in selectively transporting miRNA and disease-relevant proteins out of cells and could become a reliable and useful tool for future diagnostic, therapeutic and analytical applications.

Macrophage sensing of single-walled carbon nanotubes via Toll-like receptors.

Carbon-based nanomaterials including carbon nanotubes (CNTs) have been shown to trigger inflammation. However, how these materials are 'sensed' by immune cells is not known. Here we compared the effects of two carbon-based nanomaterials, single-walled CNTs (SWCNTs) and graphene oxide (GO), on primary human monocyte-derived macrophages. Genome-wide transcriptomics assessment was performed at sub-cytotoxic doses. Pathway analysis of the microarray data revealed pronounced effects on chemokine-encoding genes in macrophages exposed to SWCNTs, but not in response to GO, and these results were validated by multiplex array-based cytokine and chemokine profiling. Conditioned medium from SWCNT-exposed cells acted as a chemoattractant for dendritic cells. Chemokine secretion was reduced upon inhibition of NF-κB, as predicted by upstream regulator analysis of the transcriptomics data, and Toll-like receptors (TLRs) and their adaptor molecule, MyD88 were shown to be important for CCL5 secretion. Moreover, a specific role for TLR2/4 was confirmed by using reporter cell lines. Computational studies to elucidate how SWCNTs may interact with TLR4 in the absence of a protein corona suggested that binding is guided mainly by hydrophobic interactions. Taken together, these results imply that CNTs may be 'sensed' as pathogens by immune cells.

Hollow silica capsules for amphiphilic transport and sustained delivery of antibiotic and anticancer drugs.

Hollow mesoporous silica capsules (HMSC) are potential drug transport vehicles due to their biocompatibility, high loading capacity and sufficient stability in biological milieu. Herein, we report the synthesis of ellipsoid-shaped HMSC (aspect ratio ∼2) performed using hematite particles as solid templates that were coated with a conformal silica shell through cross-condensation reactions. For obtaining hollow silica capsules, the iron oxide core was removed by acidic leaching. Gas sorption studies on HMSC revealed mesoscopic pores (main pore width ∼38 Å) and a high surface area of 308.8 m2 g-1. Cell uptake of dye-labeled HMSC was confirmed by incubating them with human cervical cancer (HeLa) cells and analyzing the internalization through confocal microscopy. The amphiphilic nature of HMSC for drug delivery applications was tested by loading antibiotic (ciprofloxacin) and anticancer (curcumin) compounds as model drugs for hydrophilic and hydrophobic therapeutics, respectively. The versatility of HMSC in transporting hydrophilic as well as hydrophobic drugs and a pH dependent drug release over several days under physiological conditions was demonstrated in both cases by UV-vis spectroscopy. Ciprofloxacin-loaded HMSC were additionally evaluated towards Gram negative (E. coli) bacteria and demonstrated their efficacy even at low concentrations (10 µg ml-1) in inhibiting complete bacterial growth over 18 hours.