Effectuation of loading a natural acetyl carnosine derivative within a promising cross-linked cyclodextrin spongey-like nanospheres on Physicochemical characterization and release behavior.

This study centered on the ability of the cross-linked nano-sponge system to load the drug and to improve its physicochemical and dissolution properties. A spectrophotometric method was used to determine the wavelength of maximum absorbance of the drug. The ultrasonic-assisted synthesis method was used for nano-sponge preparation. Solution-state interactions, encapsulation efficiency and production yield, and in-vitro release were also investigated. Nano-sponges were characterized by Transmission Electron-Microscopy (TEM), Scanning Electron-Microscopy (SEM), Fourier Transform-Infrared Spectroscopy (FT-IR), Differential Scanning Calorimetry (DSC), and X-Ray Diffractometry (X-RD) studies. The maximum absorption wavelength of N-acetyl-L-carnosine was found to be at 210 nm. Solution-state interaction studies revealed a bathochromic shift. The production yield of nano-sponges ranged from 59.58% to 72.54%. In-vitro release study showed a sustained drug release for 228 hours. TEM images showed regular spherical shapes and sizes of nano-sponges. Their average particle size ranged from 28 nm to 79.2 nm. DSC data documented the drug-polymer interactions. FT-IR determined the presence of functional groups. X-RD showed the physicochemical characteristics of nano-sponges. Proving successful development of N-acetyl-L-carnosine polymeric nano-sponge system with a suitable drug delivery over an extended period beside a noticeable improvement in the physicochemical characterization.

Double Switch Biodegradable Porous Hollow Trinickel Monophosphide Nanospheres for Multimodal Imaging Guided Photothermal Therapy.

Due to the limitation of inorganic nanomaterials in present clinical applications induced by their inherent nonbiodegradability and latent long-term side effects, we successfully prepared double switch degradable and clearable trinickel monophosphide porous hollow nanospheres (NiP PHNPs) modified with bovine serum albumin (BSA). Attributed to their acidic and oxidative double switch degradation capacities, NiP PHNPs can be effectively excreted from mice without long-term toxicity. Moreover, because of the paramagnetic and high molar extinction coefficient property resulting from the strong absorption in the second near-infrared light (NIR II) biowindow, NiP PHNPs have potential to be used for photoacoustic imaging (PAI) and T1-weighted magnetic resonance imaging (MRI) guided photothermal ablation of tumors in the NIR II biowindow. Specifically, it is interesting that the hollow structure and acidic degradation property enable NiP PHNPs to act as intelligent drug carriers with an on-demand release ability. These findings highlight the great potential of NiP PHNPs in the cancer theranostics field and inspire us to further broaden the bioapplications of transition metal phosphides.

The practical self-targeted oncolytic adenoviral nanosphere based on immuno-obstruction method via polyprotein surface precipitation technique enhances transfection efficiency for virotherapy.

Recent developments in tumour treatment had focused on virotherapies that were currently revolutionising new innovated treatment pathways. This study focused on the fabrication of oncolytic adenoviral vector (Ad) nanosphere that self-targeted at lung tumour cells (A549), utilising the immune response for upper respiratory tract infection, caused by the Ad infection. This system was dependent upon T-cell immune response, surface charge and blood metabolism. Oncolytic Ad attacked lung A549 tumour cells by incorporated its own DNA to replace A549's, the triggered immune response generated T-cells also further attack A549. Direct Ad injection was demonstrated to be lethal and prohibited in vivo. In this research a multifunctional principal using polyprotein surface precipitation technique (PSP) whist maintaining biological controls for self-assembly polyprotein Ad nanosphere both biocompatible and reproducible, was demonstrated as a result of the enhanced transfection efficiency and a successful multifunctional drug delivery system for virotherapy.

Lanthanide-Doped Photoluminescence Hollow Structures: Recent Advances and Applications.

Lanthanide-doped nanomaterials have attracted significant attention for their preeminent properties and widespread applications. Due to the unique characteristic, the lanthanide-doped photoluminescence materials with hollow structures may provide advantages including enhanced light harvesting, intensified electric field density, improved luminescent property, and larger drug loading capacity. Herein, the synthesis, properties, and applications of lanthanide-doped photoluminescence hollow structures (LPHSs) are comprehensively reviewed. First, different strategies for the engineered synthesis of LPHSs are described in detail, which contain hard, soft, self-templating methods and other techniques. Thereafter, the relationship between their structure features and photoluminescence properties is discussed. Then, niche applications including biomedicines, bioimaging, therapy, and energy storage/conversion are focused on and superiorities of LPHSs for these applications are particularly highlighted. Finally, keen insights into the challenges and personal prospects for the future development of the LPHSs are provided.

Self-Assembly of Biocompatible FeSe Hollow Nanostructures and 2D CuFeSe Nanosheets with One- and Two-Photon Luminescence Properties.

Transition metal chalcogenides are investigated for catalyst, intermediary agency, and particular optical properties because of their distinguished electron-vacancy-transfer (EVT) process toward different applications. In this work, one convenient approach for making pure-phased FeSe nanocrystals (NCs) and doped CuFeSe nanosheets (NSs) through a wet chemistry method in mixed solvents is illustrated. The surface modification of each product is realized by using a peptide molecule glutathione (GSH), in which the thiol group (-SH) is ascribed to be the in situ reducer and bonding agency between the crystalline surface and surfactant in whole constructing processes. Due to the functional groups in biological GSH, highly aggregated NCs are rebuilt in the form of an FeSe hollow structure through amino and carboxyl cross-linking functions through a spontaneous assembly procedure. Owing to the coupling procedure of Cu and Fe in the growth process, it generates enhanced EVT. Additionally, it shows the emission spectra of λEM-PL = 436 nm (FeSe) and 452 nm (CuFeSe) while λEX-PL = 356 nm, it also conveys two-photon phenomenon while λEX-PL = 720 nm. Moreover, it also shows strong off-resonant luminescence due to two-photon absorption, which should be valuable for biological applications.

Native MicroRNA Targets Trigger Self-Assembly of Nanozyme-Patterned Hollowed Nanocuboids with Optimal Interparticle Gaps for Plasmonic-Activated Cancer Detection.

The modernized use of nucleic acid (NA) sequences to drive nanostructure self-assembly has given rise to a new class of designed nanomaterials with controllable plasmonic functionalities for broad surface-enhanced Raman scattering (SERS)-based bioanalysis applications. Herein, dual usage of microRNAs (miRNAs) as both valuable cancer biomarkers and direct self-assembly triggers is identified and capitalized upon for custom-designed plasmonic nanostructures. Through strict NA hybridization of miRNA targets, Au nanospheres selectively self-assemble onto hollowed Au/Ag alloy nanocuboids with ideal interparticle distances (≈2.3 nm) for optimal SERS signaling. The intrinsic material properties of the self-assembled nanostructures further elevate miRNA detection performance via nanozyme catalytic SERS signaling cascades. This enables fM-level miR-107 detection limit within a clinically-relevant range without any molecular target amplification. The miRNA-triggered nanostructure self-assembly approach is further applied in clinical patient samples, and showcases the potential of miR-107 as a non-invasive prostate cancer diagnostic biomarker. The use of miRNA targets to drive nanostructure self-assembly holds great promise as a practical tool for miRNA detection in disease applications.

Enhanced synergistic effects from multiple iron oxide nanoparticles encapsulated within nitrogen-doped carbon nanocages for simple and label-free visual detection of blood glucose.

Hollow-structured carbon materials play a crucial role in research of biosensors, energy storage and nanomedicine as a kind of material with advantages like high surface area, tunable pore volume, excellent mechanical properties, and good biocompatibility. Herein, we developed a simple, facile and controllable method for synthesis of Fe3O4 nanoparticles encapsulated in hollow carbon nanocages (FNHCs) with SiO2 nanospheres as a sacrificial template. Owing to the unique structure of multiple Fe3O4 nanoparticles cores integrated with N-doped carbon nanocages, the as-synthesized FNHCs exhibited greatly enhanced peroxidase mimicking activity with extremely high signal-to-noise ratio of ∼91 fold. Also, it was found that the FNHCs possessed a higher peroxidase-like activity than that of other similar-structured Fe3O4 architectures (e.g. Fe3O4@C NPs). The resulting steady-state kinetic curve demonstrated the enzymatic activity of FNHCs with classic Michaelis-Menton kinetics following a ping-pong mechanism. On the basis of the superior enzymatic activity, the FNHCs performed as a high-efficiency peroxidase mimic, realizing facile, label-free, highly sensitive/selective colorimetric detection of H2O2 and glucose. Furthermore, the colorimetric sensor successfully determined glucose in patients' serum samples with high accuracy and precision, suggesting great potential for real applications.

Three-dimensional assembly of silver nanoparticles spatially confined by cellular structure of Spirulina, from nanospheres to nanosheets.

Three-dimensional (3D) ordered construction of nanoparticles (NPs) has attracted much attention in wide applications, however, techniques with respect to cost effective nanofabrication of well defined functional architectures is still lacking. To address this specific issue, a bio-interface confinement approach is proposed that precisely replicates the complex cellular structural features of microbes and integrates silver NP (SNP) building blocks into their 3D framework in a precise, low cost and mass production way. Herein, the SNPs with nanospheres and nanosheets structure were synthesized by way of electroless deposition using Spirulina as template. Results showed that SNPs were orderly assembled along the cellular structure, and the spatially confinement of cellular texture induced the transformation of SNPs from sphere to flake morphology during their continuous growth. The silver assembly not only shows good antibacterial activity, but also exhibits excellent surface enhanced Raman scattering (SERS) performance with the enhancement factor as high as 5.95 × 108 and good recuperability towards Rhodamine 6G. The fascinating SERS performance can be ascribed to the combined action of nanosheets morphology of SNPs, hierarchical nanostructure of the cellular structure, and the small interparticle spacing. This strategy provides an effective strategy for controllable and ordered 3D assembly of NPs by using the cellular texture.

Polymer Nanospheres with Hydrophobic Surface Groups as Supramolecular Building Blocks Produced by Aqueous PISA.

A robust and straightforward synthesis of waterborne polymer nanospheres bearing the supramolecular association unit dialkoxynapthalene at their surface is presented using polymerization-induced self-assembly (PISA). A RAFT agent bearing this unit is first employed to produce poly(acrylic acid) chains, which are then chain-extended with styrene (S) to spontaneously form the nano-objects via RAFT aqueous emulsion polymerization. The particular challenge posed by the dialkoxynapthalene hydrophobicity can be overcome by the use of PISA and the deprotonation of the poly(acrylic acid). At pH = 7, very homogeneous latexes are obtained. The particle diameters can be tuned from 36 to 105 nm (with a narrow particle size distribution) by varying the molar mass of the PS block. The surface accessibility of the dialkoxynapthalene moieties is demonstrated by complexation with the complementary host cyclobis(paraquat-p-phenylene) (CBPQT4+ · Cl- ), highlighting the potential of the nanospheres to act as building blocks for responsive supramolecular structures.

Nanospherical arabinogalactan proteins are a key component of the high-strength adhesive secreted by English ivy.

Over 130 y have passed since Charles Darwin first discovered that the adventitious roots of English ivy (Hedera helix) exude a yellowish mucilage that promotes the capacity of this plant to climb vertical surfaces. Unfortunately, little progress has been made in elucidating the adhesion mechanisms underlying this high-strength adhesive. In the previous studies, spherical nanoparticles were observed in the viscous exudate. Here we show that these nanoparticles are predominantly composed of arabinogalactan proteins (AGPs), a superfamily of hydroxyproline-rich glycoproteins present in the extracellular spaces of plant cells. The spheroidal shape of the AGP-rich ivy nanoparticles results in a low viscosity of the ivy adhesive, and thus a favorable wetting behavior on the surface of substrates. Meanwhile, calcium-driven electrostatic interactions among carboxyl groups of the AGPs and the pectic acids give rise to the cross-linking of the exuded adhesive substances, favor subsequent curing (hardening) via formation of an adhesive film, and eventually promote the generation of mechanical interlocking between the adventitious roots of English ivy and the surface of substrates. Inspired by these molecular events, a reconstructed ivy-mimetic adhesive composite was developed by integrating purified AGP-rich ivy nanoparticles with pectic polysaccharides and calcium ions. Information gained from the subsequent tensile tests, in turn, substantiated the proposed adhesion mechanisms underlying the ivy-derived adhesive. Given that AGPs and pectic polysaccharides are also observed in bioadhesives exuded by other climbing plants, the adhesion mechanisms revealed by English ivy may forward the progress toward understanding the general principles underlying diverse botanic adhesives.

Preparation of a Novel Lignin Nanosphere Adsorbent for Enhancing Adsorption of Lead.

Carboxymethyl lignin nanospheres (CLNPs) were synthesized by a two-step method using microwave irradiation and antisolvent. The morphology and structure of CLNPs were characterized by 31P-NMR, FTIR, and SEM, and the results showed that they had an average diameter of 73.9 nm, a surface area of 8.63 m2 or 3.2 times larger than the original lignin, and abundant carboxyl functional groups of 1.8 mmol/g. The influence of dosage, pH, contact time, and concentration on the adsorption of metal ions onto CLNPs were analyzed, and the maximum adsorption capacity of CLNPs for Pb(II) was found to be 333.26 mg/g, which is significantly higher than other lignin-based adsorbents and conventional adsorbents. Adsorption kinetics and isotherms indicated that the adsorption of lead ions in water onto CLNPs followed the pseudo-second-order model based on monolayer chemisorption mechanism. The main chemical interaction between CLNPs and lead ions was chelation. CLNPs also showed an excellent recycling performance, with only 27.0% adsorption capacity loss after 10 consecutive adsorption-desorption cycles.

Magnetic chitosan/sodium alginate gel bead as a novel composite adsorbent for Cu(II) removal from aqueous solution.

Using sodium alginate hydrogel as skeleton, in combination with chitosan and magnetic Fe3O4, a new type of magnetic chitosan/sodium alginate gel bead (MCSB) was prepared. Adsorptive removal of Cu(II) from aqueous solutions was studied by using the MCSB as a promising candidate in environmental application. Different kinetics and isotherm models were employed to investigate the adsorption process. Based on Fourier transform infrared spectroscopy, field-emission scanning electron microscope, CHNS/O elements analysis, vibration magnetometer, and various means of characterization, a comprehensive analysis of the adsorption mechanism was conducted. The MCSB had a good magnetic performance with a saturation magnetization of 12.5 emu/g. Elemental analysis proved that the addition of chitosan introduced a considerable amount of nitrogen-rich groups, contributing significantly to copper adsorption onto gel beads. The contact time necessary for adsorption was optimized at 120 min to achieve equilibrium. Experimental data showed that the adsorption process agreed well with the Langmuir isotherm model and the pseudo-second-order kinetics model. The theoretical maximum adsorption capacity of MCSB for Cu(II) could reach as high as 124.53 mg/g. In conclusion, the MCSB in this study is a novel and promising composite adsorbent, which can be applied for practical applications in due course.

Near-Infrared Light-Excited Core-Core-Shell UCNP@Au@CdS Upconversion Nanospheres for Ultrasensitive Photoelectrochemical Enzyme Immunoassay.

A novel photoelectrochemical (PEC) enzyme immunoassay was designed for the ultrasensitive detection of alpha-fetoprotein (AFP) based on near-infrared (NIR) light-excited core-core-shell UCNP@Au@CdS upconversion nanospheres. Plasmonic gold (Au) between the sandwiched layers was not only utilized as an energy harvester for the collection of the incident light but also acted as an energy conveyor to transfer the energy from upconversion NaYF4:Yb3+,Er3+ (UCNP) to semiconductor CdS, thus exciting the efficient separation of electron-hole pairs by the generated H2O2 of enzyme immunoreaction under the irradiation of a 980 nm laser. By virtue of high catalytic activity of natural enzymes, gold nanoparticles heavily functionalized with glucose oxidase (GOx) and polyclonal anti-AFP antibody were utilized to generate H2O2. A sandwiched immunoreaction was first carried out in a monoclonal anti-AFP antibody-coated microplate by using an antibody-labeled gold nanoparticle as secondary antibody. Accompanying the gold nanoparticle, the carried GOx oxidized glucose in H2O2, thereby resulting in the enhanced photocurrent via capturing holes on the valence band of CdS to promote the separation of electron-hole pairs. Under optimum conditions, the NIR light-based PEC immunosensing system exhibited good photocurrent responses toward target AFP within the dynamic working range of 0.01-40 ng mL-1 at a detection limit of 5.3 pg mL-1. Moreover, the NIR light-based sensing platform had good reproducibility and high selectivity. Importantly, good well-matched results obtained from NIR light-based PEC immunoassay were acquired for the analysis of human serum specimens by using AFP ELISA kit as the reference.

Polydopamine Nanosphere/Gold Nanocluster (Au NC)-Based Nanoplatform for Dual Color Simultaneous Detection of Multiple Tumor-Related MicroRNAs with DNase-I-Assisted Target Recycling Amplification.

A novel fluorescence resonance energy transfer (FRET)-based platform using polydopamine nanospheres (PDANSs) as energy acceptors and dual colored Au NCs as energy donors for simultaneous detection of multiple tumor-related microRNAs with DNase-I-assisted target recycling amplification was developed for the first time. On the basis of monitoring the change of the recovered fluorescence intensity at 445 and 575 nm upon the addition of targets miRNA-21 and let-7a, these two microRNAs (miRNAs) can be simultaneously quantitatively detected, with detection limits of 4.2 and 3.6 pM (3σ) for miRNA-21 and let-7a, which was almost 20 times lower than that without DNase I. Additionally, semiquantitative determination of miRNA-21 and let-7a can also be realized through photovisualization. Most importantly, serums from normal and breast cancer patients can be visually and directly discriminated without any sample pretreatment by confocal microscope experiments, demonstrating promising potential for auxiliary clinical diagnosis.

Bottom-up synthesis of MoS2 nanospheres for photothermal treatment of tumors.

Photothermal therapy (PTT) is providing new opportunities for killing cancer cells. In this work, we introduce a new nanomedicine based on spherical MoS2 nanoparticles for PTT treatment of tumors, prepared using "green" bottom-up technology. To increase water solubility and avoid rapid clearance by the reticuloendothelial system, polyethylene glycol (PEG) was used to coat them. These MoS2-PEG nanospheres with an appropriate size (∼100 nm) exhibit high photothermal conversion efficiency (26.7%). In vitro cellular studies revealed that the MoS2-PEG nanospheres showed negligible cytotoxicity. Additionally, through combining the MoS2-PEG nanosphere samples with NIR irradiation at 808 nm, excellent in vitro tumor cell killing efficacy was achieved. In the 4T1 tumor model, the MoS2-PEG nanospheres exhibited good antitumor efficiency in vivo, displaying complete tumor inhibition over 16 days after treatment. Therefore, MoS2-PEG nanospheres played an important role in tumor destruction, and this concept for developing spherical MoS2-based nanomedicines can serve as a platform technology for the next generation of in vivo PTT agents.

Copper oxide loaded PLGA nanospheres: towards a multifunctional nanoscale platform for ultrasound-based imaging and therapy.

Copper oxide nanoparticles (CuO-NPs) are increasingly becoming the subject of investigation exploring their potential use for diagnostic and therapeutic purposes. Recent work has demonstrated their anticancer potential, as well as contrast agent capabilities for magnetic resonance imaging (MRI) and through-transmission ultrasound. However, no capability of CuO-NPs has been demonstrated using conventional ultrasound systems, which, unlike the former, are widely deployed in the clinic. Furthermore, in spite of their potential as multifunctional nano-based materials for diagnosis and therapy, CuO-NPs have been delayed from further clinical application due to their inherent toxicity. Herein, we present the synthesis of a novel nanoscale system, composed of CuO-loaded PLGA nanospheres (CuO-PLGA-NS), and demonstrate its imaging detectability and augmented heating effect by therapeutic ultrasound. The CuO-PLGA-NS were prepared by a double emulsion (W/O/W) method with subsequent solvent evaporation. They were characterized as sphere-shaped, with size approximately 200 nm. Preliminary results showed that the viability of PANC-1, human pancreatic adenocarcinoma cells was not affected after 72 h exposure to CuO-PLGA-NS, implying that PLGA masks the toxic effects of CuO-NPs. A systematic ultrasound imaging evaluation of CuO-PLGA-NS, using a conventional system, was performed in vitro and ex vivo using poultry heart and liver, and also in vivo using mice, all yielding a significant contrast enhancement. In contrast to CuO-PLGA-NS, neither bare CuO-NPs nor blank PLGA-NS possess these unique advantageous ultrasonic properties. Furthermore, CuO-PLGA-NS accelerated ultrasound-induced temperature elevation by more than 4 °C within 2 min. The heating efficiency (cumulative equivalent minutes at 43 °C) was increased approximately six-fold, demonstrating the potential for improved ultrasound ablation. In conclusion, CuO-PLGA-NS constitute a versatile platform, potentially useful for combined imaging and therapeutic ultrasound-based procedures.

Sol-gel TiO2 colloidal suspensions and nanostructured thin films: structural and biological assessments.

The role of substrate topography in phenotype expression of in vitro cultured cells has been widely assessed. However, the production of the nanostructured interface via the deposition of sol-gel synthesized nanoparticles (NPs) has not yet been fully exploited. This is also evidenced by the limited number of studies correlating the morphological, structural and chemical properties of the grown thin films with those of the sol-gel 'brick' within the framework of the bottom-up approach. Our work intends to go beyond this drawback presenting an accurate investigation of sol-gel TiO2 NPs shaped as spheres and rods. They have been fully characterized by complementary analytical techniques both suspended in apolar solvents, by dynamic light scattering (DLS) and nuclear magnetic resonance (NMR) and after deposition on substrates (solid state configuration) by transmission electron microscopy (TEM) and powder x-ray diffraction (PXRD). In the case of suspended anisotropic rods, the experimental DLS data, analyzed by the Tirado-Garcia de la Torre model, present the following ranges of dimensions: 4-5 nm diameter (∅) and 11-15 nm length (L). These results are in good agreement with that obtained by the two solid state techniques, namely 3.8(9) nm ∅ and 13.8(2.5) nm L from TEM and 5.6(1) ∅ and 13.3(1) nm L from PXRD data. To prove the suitability of the supported sol-gel NPs for biological issues, spheres and rods have been separately deposited on coverslips. The cell response has been ascertained by evaluating the adhesion of the epithelial cell line Madin-Darby canine kidney. The cellular analysis showed that titania films promote cell adhesion as well clustering organization, which is a distinguishing feature of this type of cell line. Thus, the use of nanostructured substrates via sol-gel could be considered a good candidate for cell culture with the further advantages of likely scalability and interfaceability with many different materials usable as supports.

3D bioprinting mesenchymal stem cell-laden construct with core-shell nanospheres for cartilage tissue engineering.

Cartilage tissue is prone to degradation and has little capacity for self-healing due to its avascularity. Tissue engineering, which provides artificial scaffolds to repair injured tissues, is a novel and promising strategy for cartilage repair. 3D bioprinting offers even greater potential for repairing degenerative tissue by simultaneously integrating living cells, biomaterials, and biological cues to provide a customized scaffold. With regard to cell selection, mesenchymal stem cells (MSCs) hold great capacity for differentiating into a variety of cell types, including chondrocytes, and could therefore be utilized as a cartilage cell source in 3D bioprinting. In the present study, we utilize a tabletop stereolithography-based 3D bioprinter for a novel cell-laden cartilage tissue construct fabrication. Printable resin is composed of 10% gelatin methacrylate (GelMA) base, various concentrations of polyethylene glycol diacrylate (PEGDA), biocompatible photoinitiator, and transforming growth factor beta 1 (TGF-ß1) embedded nanospheres fabricated via a core-shell electrospraying technique. We find that the addition of PEGDA into GelMA hydrogel greatly improves the printing resolution. Compressive testing shows that modulus of the bioprinted scaffolds proportionally increases with the concentrations of PEGDA, while swelling ratio decreases with the increase of PEGDA concentration. Confocal microscopy images illustrate that the cells and nanospheres are evenly distributed throughout the entire bioprinted construct. Cells grown on 5%/10% (PEGDA/GelMA) hydrogel present the highest cell viability and proliferation rate. The TGF-ß1 embedded in nanospheres can keep a sustained release up to 21 d and improve chondrogenic differentiation of encapsulated MSCs. The cell-laden bioprinted cartilage constructs with TGF-ß1-containing nanospheres is a promising strategy for cartilage regeneration.

The Formation of Calcified Nanospherites during Micropetrosis Represents a Unique Mineralization Mechanism in Aged Human Bone.

Osteocytes-the central regulators of bone remodeling-are enclosed in a network of microcavities (lacunae) and nanocanals (canaliculi) pervading the mineralized bone. In a hitherto obscure process related to aging and disease, local plugs in the lacuno-canalicular network disrupt cellular communication and impede bone homeostasis. By utilizing a suite of high-resolution imaging and physics-based techniques, it is shown here that the local plugs develop by accumulation and fusion of calcified nanospherites in lacunae and canaliculi (micropetrosis). Two distinctive nanospherites phenotypes are found to originate from different osteocytic elements. A substantial deviation in the spherites' composition in comparison to mineralized bone further suggests a mineralization process unlike regular bone mineralization. Clearly, mineralization of osteocyte lacunae qualifies as a strong marker for degrading bone material quality in skeletal aging. The understanding of micropetrosis may guide future therapeutics toward preserving osteocyte viability to maintain mechanical competence and fracture resistance of bone in elderly individuals.

Hollow Carbon Nanospheres with Tunable Hierarchical Pores for Drug, Gene, and Photothermal Synergistic Treatment.

Design and synthesis of porous and hollow carbon spheres have attracted considerable interest in the past decade due to their superior physicochemical properties and widespread applications. However, it is still a big challenge to achieve controllable synthesis of hollow carbon nanospheres with center-radial large mesopores in the shells and inner surface roughness. Herein, porous hollow carbon nanospheres (PHCNs) are successfully synthesized with tunable center-radial mesopore channels in the shells and crater-like inner surfaces by employing dendrimer-like mesoporous silica nanospheres (DMSNs) as hard templates. Compared with conventional mesoporous nanospheres, DMSN templates not only result in the formation of center-radial large mesopores in the shells, but also produce a crater-like inner surface. PHCNs can be tuned from open center-radial mesoporous shells to relatively closed microporous shells. After functionalization with polyethyleneimine (PEI) and poly(ethylene glycol) (PEG), PHCNs not only have negligible cytotoxicity, excellent photothermal property, and high coloading capacity of 482 µg of doxorubicin and 44 µg of siRNA per mg, but can also efficiently deliver these substances into cells, thus displaying enhanced cancer cell killing capacity by triple-combination therapy.