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Transistors made up of carbon nanotube CNT have demonstrated excellent current–voltage characteristics which outperform some high-grade silicon-based transistors. A continuously tunable energy barrier across semiconductor interfaces is desired to make the CNT-based transistors more robust. Despite that the direct band gap of the carbyne inside a CNT can be widely tuned by strain, the size of the carbyne cannot be controlled easily. The production of a monoatomic chain with more than 6000 carbon atoms is an enormous technological challenge. To predict the optimal chain length of a carbyne in different molecular environments, we have developed a Monte Carlo model in which a finite-length carbyne with a size of 4000–15,000 atoms is encapsulated by a CNT at finite temperatures. Our simulation shows that the stability of the carbyne@nanotube is strongly influenced by the nature and porosity of the CNT, the external pressure, the temperature, and the chain length. We have observed an initiation of the chain-breaking process in a compressed carbyne@nanotube. Our work provides much-needed input for optimizing the carbyne length to produce carbon chains much longer than 6000 atoms at ~300 K. Design rules are proposed for synthesizing ~1% strained carbyne@(6,5)CNT as a component in CNT-based transistors to tune the energy barriers continuously.

Understanding the morphology and hemodynamics of cerebral vasculature at large penetration depths and microscale resolution is fundamentally important to decipher brain diseases. Among the various imaging technologies, three-photon (3P) microscopy is of significance by virtue of its deep-penetrating capability and submicron resolution, which especially benefitsiin vivo/ivascular imaging. Aggregation-induced emission luminogens (AIEgens) have been recognized to be extraordinarily powerful as 3P probes. However, systematic studies on the structure-performance relationship of 3P AIEgens have been seldom reported. Herein, a series of AIEgens has been designed and synthesized. By intentionally introducing benzene rings onto electron donors (D) and acceptors (A), the molecular distortion, conjugation strength, and the D-A relationship can be facilely manipulated. Upon encapsulation with DSPE-PEGsub2000/sub, the optimized AIEgens are successfully applied for 3P microscopy with emission in the far-red/near-infrared-I (NIR-I, 700-950 nm) region under the near-infrared-III (NIR-III, 1600-1870 nm) excitation. Impressively, using mice with an opened skull, vasculature within 1700 μm and a microvessel with a diameter of 2.2 μm in deep mouse brain were clearly visualized. In addition, the hemodynamics of blood vessels were well-characterized. Thus, this work not only proposes a molecular design strategy of 3P AIEgens but also promotes the performance of 3P imaging in cerebral vasculature.

Gene therapy has shown great potential in the treatment of many diseases by downregulating the expression of certain genes. The development of gene vectors as a vehicle for gene therapy has greatly facilitated the widespread clinical application of nucleic acid materials (DNA, mRNA, siRNA, and miRNA). Currently, both viral and non-viral vectors are used as delivery systems of nucleic acid materials for gene therapy. However, viral vector-based gene therapy has several limitations, including immunogenicity and carcinogenesis caused by the exogenous viral vectors. To address these issues, non-viral nanocarrier-based gene therapy has been explored for superior performance with enhanced gene stability, high treatment efficiency, improved tumor-targeting, and better biocompatibility. In this review, we discuss various non-viral vector-mediated gene therapy approaches using multifunctional biodegradable or non-biodegradable nanocarriers, including polymer-based nanoparticles, lipid-based nanoparticles, carbon nanotubes, gold nanoparticles (AuNPs), quantum dots (QDs), silica nanoparticles, metal-based nanoparticles and two-dimensional nanocarriers. Various strategies to construct non-viral nanocarriers based on their delivery efficiency of targeted genes will be introduced. Subsequently, we discuss the cellular uptake pathways of non-viral nanocarriers. In addition, multifunctional gene therapy based on non-viral nanocarriers is summarized, in which the gene therapy can be combined with other treatments, such as photothermal therapy (PTT), photodynamic therapy (PDT), immunotherapy and chemotherapy. We also provide a comprehensive discussion of the biological toxicity and safety of non-viral vector-based gene therapy. Finally, the present limitations and challenges of non-viral nanocarriers for gene therapy in future clinical research are discussed, to promote wider clinical applications of non-viral vector-based gene therapy.

Cancer is a life-threatening disease worldwide. Although several approaches, such as surgery, chemotherapy, and radiotherapy, have been proven effective for many patients in clinics, they usually suffer from drug resistance, severe toxic-side effects, patient discomfort, and sometimes, unsatisfactory efficacies. In recent years, phototherapy, as a less invasive but effective therapeutic method, has brought hope for cancer treatment. However, most reported photo-therapeutic agents are constructed using complex components with non-negligible toxicity risk, thus retarding the start of their clinical trials. To address this issue, herein, biocompatible photothermal/photodynamic dual-mode therapeutic nanoparticles (CBP NPs) were successfully designed and constructed based on the Food and Drug Administration (FDA)-approved ingredients, chlorin e6 (Ce6) and poly(dopamine) (PDA). Upon light irradiation, hyperthermia was induced and reactive oxygen species (ROS) were generated simultaneously by CBP NPs, contributing to synergistic phototherapy toward cancer. The

Photodynamic efficiency is strongly dependent on the generation rate of reactive oxygen species (ROS) and the tissue penetration depth. Recent advances in materials science reveal that organic molecules with room-temperature phosphorescence (RTP) can potentially serve as efficient photosensitizers owing to their limited dark cytotoxicity and abundant triplet excitons upon light irradiation. In this study, we combine RTP materials with two-photon excitation to improve the ROS generation, therapeutic precision, and tissue penetration of photodynamic therapy. We successfully prepared a novel RTP-based photosensitizer (BF

Nowadays, energy and the environment have become critical issues for determining the sustainability of the Earth. Freshwater crises, as an increasingly serious global problem, pose a great threat to our economies, the environment and us. Solar-driven evaporation has emerged as a promising and sustainable approach to convert solar energy into clean water. In fact, the production of freshwater is not only governed by heat generation at the interface, but the process also relies on the coordination and cooperation of functional modules in the solar-driven evaporation system. This review begins with system designs of solar evaporators, considering thermal manipulation structures, water transportation pathways, and vapour condensation modules, which focus on improving the overall energy utilization, long-term usability, and freshwater yield. This is followed by a summary and discussions of cutting-edge solar evaporation applications and their underlying mechanisms. Finally, existing challenges and potential solutions for future applications are discussed and provided. This review aims to provide useful guidelines and references to scientists and researchers for the future development of clean water generation systems.

This paper presents a comprehensive study of the energy structure, optical characteristics, and spectral-kinetic parameters of elementary excitations in a high-purity nanocrystalline cubic Y2O3 film synthesized by reactive magnetron sputtering. The optical transparency gaps for direct and indirect interband transitions were determined and discussed. The dispersion of the refractive index was established based on the analysis of interference effects. It was found that the refractive index of the Y2O3 film synthesized in this study is higher in order of magnitude than that of the films obtained with the help of other technologies. The intrinsic emission of Y2O3 film has been discussed and associated with the triplet–singlet radiative relaxation of self-trapped and bound excitons. We also studied the temperature behavior of the exciton luminescence of Y2O3 for the first time and determined thermal activation barriers. The optical energy and kinetic parameters of cubic Y2O3 films were analyzed in comparison with those of the monoclinic films of yttrium oxide. The main difference between the optical properties of cubic and monoclinic Y2O3 films was established, which allowed for a supposition of their application prospects. © 2022 by the authors. Ministry of Education and Science of the Russian Federation, Minobrnauka: 4.38 The work was supported by the Ministry of Science and Higher Education of the Russian Federation (Ural Federal University Program of Development within the Priority-2030 Program, project № 4.38). We thank the Research Institute for Advanced Manufacturing and the Industrial Centre of The Hong Kong Polytechnic University for support.

Four-dimensional (4D) printable light-powered materials have emerged as a new generation of materials for the development of functional devices. The design of these types of materials is mostly based on the trans-cis transformation of azobenzene moieties in a liquid crystalline elastomer (LCE) matrix, in which the motion is triggered by ultraviolet (UV) irradiation. In this paper, we first report on a direct laser printable photoresist for producing light-powered 4D structures with enhanced mechanical properties and near-infrared (NIR) responsive mechanical deformation. The reported nanocomposite design is based on the photothermal effects of gold nanorods (AuNRs), which can induce the nematic-to-isotropic transition of LCE upon exposure to NIR irradiation. The miscibility between AuNRs and LCE is enhanced by thiol functionalization. Appropriate printing parameters are determined, and nanocomposites containing 0-3 wt % of AuNR loading are fabricated via femtosecond two-photon direct laser writing. The effects of the AuNR loading fraction and laser power on the light-powered actuating performance are evaluated. It is found that the nanocomposite with AuNR loading of 3 wt % demonstrates the maximum percentage (20%) of elongation under an NIR laser power of 2 W. An increase in laser power can lead to faster deformation but slower restoration. The nanocomposites demonstrate relatively good stability. Even after 300 actuation cycles, 80% of the elongation magnitude can be retained. In addition, an improvement of 80% in the complex modulus of the nanocomposites, due to the inclusion of AuNRs, is observed.

Consumer grade supercapacitors as power supply resources require outstanding electrode materials with large conductivity, high durability and retention rates, as well as large capacity. Graphene is a promising functional material as an electrical double layer capacitance electrode due to its large surface area, high chemical stability and moderate conductivity. However, the existing graphene synthesis methods, including CVD and chemical exfoliation, are limited to lab scale production. Although laser induced graphene has demonstrated outstanding performance as an electrode material for microsupercapacitors, its difficulty to attach to the metallic current collector limits its application as a large capacity electrode material. Herein, laser induced forward transfer of graphene is developed for additively depositing laser induced graphene onto nickel foam as a composite electrode. The laser annealing enhanced the lattice matching between the extended Basal plane of graphene and Ni (111) resulting in its high electrical conductivity (359 712 S m−1), high retention rate (over 98% capacitance retention after 10 000 cycles), and large areal specific capacitance (995 mF cm−2) and power density (9.39 mW cm−2). The assembled supercapacitors with these additively printed electrodes can work as a USB charger with a stable 5 V output voltage, for charging smart phones and other smart devices.

Wearable sensing technologies are vital for realizing personalized health monitoring. Noninvasive human sweat sampling is essential for monitoring an individual's physical state using rich physiological data. However, existing wearable sensing technologies lack the controlled capture of body sweat and in performing on-device measurement without inflammatory contact. Herein, we report the development of a wearable sweat-capture device using patterned graphene arrays with controlled superwettability and electrical conductivity for simultaneously capturing and electrochemically measuring sweat droplets. The sweat droplets exhibited strong attachment on the superhydrophilic graphene patterns, even during moderate exercising. The captured sweat droplets present strong electrochemical signals using graphene films as the working electrode and metal pins as the counter electrode arrays assembled on 3D printed holders, at the detection limit of 6 μM for H2O2 sensing. This research enables full-body spatiotemporal mapping of sweat, which is beneficial for a broad range of personalized monitoring applications, such as drug abuse detection, athletics performance optimization, and physiological wellness tracking.

Powder metallurgy and rapid microwave (MW) sintering techniques were successfully applied to engineer a hybrid cell structure into magnesium alloy AZ61 syntactic foams. The hybrid cell structure, comprising open- and closed-cells, originated from leached carbamide granules and hollow microspheres of fly ash (HS), respectively. External MW susceptors accelerated the sintering process and greatly mitigated the formation of undesirable interfacial reactions. The cell hybridisation technique facilitated control over the density and strength of the syntactic foams. Accordingly, floatable syntactic foams with a density of about 0.79 g/cm3 and compressive strength of 16 MPa were synthesised without recourse to any surface modification or chemically-induced superhydrophobicity. The processing techniques were capable of mitigating damage to the HS microspheres as confirmed by microstructural examinations. Furthermore, potential applications of the floatable syntactic foam sample, as a microboat and chemical release agent, were demonstrated by using ethanol as a propellant. AZ61 syntactic foams synthesised in this study exhibited low density and adequate strength, suggesting their applicability as alternative materials to polymer composite foams. Keywords: Magnesium alloy, Powder metallurgy, Microwave sintering, Mechanical properties, Syntactic foam, Hybrid cells

The present study proposes an efficient processing scheme for fabricating carbon nanotubes (CNTs)-reinforced magnesium (Mg) alloy AZ61 composite foams with enhanced compressive and energy absorption properties. The scheme combines powder metallurgy, rapid microwave (MW) sintering, and pore wall reinforcement to overcome the low strength, non-uniform pore structure, prolonged sintering process, and high production cost associated with conventional unreinforced Mg-based foams. In the proposed scheme, a dual-stage mixing method is used to homogeneously disperse and incorporate CNTs into the matrix for strength enhancement, and susceptor role, and carbamide granules are used to control the pore size and porosity fractions. In addition, MW sintering is used to rapidly consolidate the samples in 20 min through the synergy between an external and an internal susceptor (i.e. CNTs), which facilitates uniform and volumetric heating of the entire samples. Thus, sample oxidation and the formation of deleterious secondary phases are minimised, while up to 69% energy is saved. Experimental results show that the dispersion and incorporation of CNTs into the matrix, via the present processing scheme, clearly enhance the compressive and energy absorption properties of the composite foams, as compared with the unreinforced foams. The proposed processing scheme is a rapid and energy-saving efficient technique, which can be used to fabricate high quality Mg alloy composite foams with improved compression and energy absorption properties.

Finite element modelling of a magnesium alloy matrix filled with a 2% volume fraction of carbon nanotubes (CNT) under 2.45 GHz microwave (MW) irradiation is reported. The effective dielectric and permeability data of the simulated compact are evaluated using the effective medium approximation. Subsequently, these values are used to solve Maxwell’s electromagnetic equations followed by the heat conduction equation, thus both the field distribution in the oven cavity and the predicted heating of the model compact are obtained. At an applied power of 1 kW and a 9-minute simulation time, the results show poor coupling between the monolithic metal compact and the MW, resulting in a maximum temperature of ~163 °C. It is in good agreement with earlier studies and theory in which metals did not couple very well with MWs at room temperatures. The model also predicts the temperature in the 2% CNT-filled alloy compact to be 13 °C higher than in the monolithic compact after a similar simulated microwave irradiation duration. Furthermore, the effect of susceptor-assisted microwave heating is investigated by introducing a susceptor kiln into the model. Simulation results predict the temperature of the compact to rise to about 600 °C after 9 minutes, highlighting the importance of susceptor-assisted sintering. The model developed is significant in providing important details for predicting the response of metal compacts and their composites to MW heating as well as further improving the development of MW technology for the production of materials with enhanced properties.

First-line therapy of chronic myelogenous leukemia (CML) has always involved the use of BCR-ABL tyrosine-kinase inhibitors which is associated with an abnormal chromosome called Philadelphia chromosome. Although the overall survival rate has been improved by the current therapeutic regime, the presence of resistance has resulted in limited efficacy. In this study, an RNA interference (RNAi)-based therapeutic regime is proposed with the aim to knockdown the BCR-ABL hybrid oncogene using small interfering RNA (siRNA). The siRNA transfection rates have usually been limited due to the declining contact probability among polyplexes and the non-adherent nature of leukemic cells. Our work aims at addressing this limitation by using a biodegradable charged polyester-based vector (BCPV) as a nanocarrier for the delivery of BCR-ABL-specific siRNA to the suspension culture of a K562 CML cell line. BCR-ABL siRNAs were encapsulated in the BCPVs by electrostatic force. Cell internalization was facilitated by the BCPV and assessed by confocal microscopy and flow cytometry. The regulation of the BCR-ABL level in K562 cells as a result of RNAi was analyzed by real-time polymerase chain reaction (RT-PCR). We observed that BCPV was able to form stable nanoplexes with siRNA molecules, even in the presence of fetal bovine serum (FBS), and successfully assisted in vitro siRNA transfection in the non-adherent K562 cells. As a consequence of downregulation of BCR-ABL, BCPV-siRNA nanoplexes inhibited cell proliferation and promoted cell apoptosis. All results were compared with a commercial transfection reagent, Lipofectamine2000™, which served as a positive control. More importantly, this class of non-viral vector exhibits biodegradable features and negligible cytotoxicity, thus providing a versatile platform to deliver siRNA to non-adherent leukemia cells with high transfection efficiency by effectively overcoming extra- and intra-cellular barriers. Due to the excellent in vitro transfection results from BCPV-siRNA, a newly developed biodegradable transfection agent, BCPV, is being probed for transfection performance in an animal model.

Composite materials, such as organic matrices doped with inorganic fillers, can generate new properties that exhibit multiple functionalities. In this paper, an epoxy-based nanocomposite that has a high thermal conductivity and a low electrical conductivity, which are required for the use of a material as electronic packaging and insulation, was prepared. The performance of the epoxy was improved by incorporating a magnesium oxide-coated graphene (MgO@GR) nanomaterial into the epoxy matrix. We found that the addition of a MgO coating not only improved the dispersion of the graphene in the matrix and the interfacial bonding between the graphene and epoxy but also enhanced the thermal conductivity of the epoxy while preserving the electrical insulation. By adding 7 wt % MgO@GR, the thermal conductivity of the epoxy nanocomposites was enhanced by 76% compared with that of the neat epoxy, and the electrical resistivity was maintained at 8.66 × 10(14) Ω m.

In this paper, a new method for preparing hyaluronic acid-quantum dot (HA-QD) nanohybrids, which are highly monodispersed, colloidally stable, glutathione (GSH)-responsive and size tunable from 80-500 nm, is reported. Due to the fact that HA is a naturally exist polymer and many types of cancer cells are overexpressed with HA receptors on their surfaces, HA has become one of the promising materials to prepare nanocarriers for theranostics applications. Our design is based on the disulfide chemical structure of cystamine dihydrochloride which has been served as the crosslinker. HA-QDs were synthesized in the nano-cavities created by the microemulsion system. The prepared HA-QDs are GSH-responsive. In the presence of GSH, the disulfide bonds can be cleaved and it leads to the degradation of HA-QDs into smaller fragments. Our in vitro studies show that the HA-QDs are highly specific to the pancreatic and cervix cancer cells and no toxicity was detected in the cell proliferation (MTS) assays, revealing the great potentials to use HA-based nanohybrids for cancer imaging and therapy.

We have developed aggregation-induced emission (AIE) dye loaded polymer nanoparticles with deep-red emission for siRNA delivery to pancreatic cancer cells. Two US Food and Drug Administration (FDA) approved surfactant polymers, Pluronics F127 and PEGylated phospholipid, were used to prepare the dye-loaded nanoparticle formulations and they can be used as nanovectors for gene silencing of mutant K-ras in pancreatic cancer cells. The successful transfection of siRNA by the developed nanovectors was confirmed by the fluorescent imaging and quantified through flow cytometry. Quantitative real time polymerase chain reaction (PCR) indicates that the expression of the mutant K-ras oncogene from the MiaPaCa-2 pancreatic cancer cells has been successfully suppressed. More importantly, our in vivo toxicity study has revealed that both the nanoparticle formulations are highly biocompatible in BALC/c mice. Overall, our results suggest that the AIE dye-loaded polymer nanoparticle formulations developed here are suitable for gene delivery and have high potential applications in translational medicine research.

Single point diamond tools are commonly used for ultraprecision machining. At high cutting speeds, frictional contact and local heat may cause material damage to the diamond tool. The diamond crystal is softened and its mechanical strength decreases with the increase in temperature. Plastic deformation of diamonds was recently reported in some experimental studies. In this work, a molecular dynamics (MD) simulation was implemented to predict the deformation of single crystal diamond at various temperatures. Diamond is brittle at room temperature, however, it starts to exhibit plastic dislocation at a temperature above 1200 K under a confining pressure. The condition in ultraprecision machining is indeed a temperature gradient distribution at the tool tip, between the maximum temperature at the tool-workpiece interface and the average temperature at the core. The simulation results predicted that diamond deformed plastically under the gradient between 1500K and 860K. It is surprising that secondary cracks were resulted from the gradient, as comparing to a single slip obtained in an evenly distributed temperature. Bond dissociation nucleated the fractures along the (111) shuffle planes, perfect dislocation merely occurred in the hot zone and sp3-to-sp2 disorder at the cool zone. The temperature gradient created a lattice mismatch and nucleated the secondary cracks. The results give an insight that a catastrophic fracture and local material damage can occur at a diamond tool tip at the cutting temperature above 1200 K, due to softening and graphitization.

Infectious diseases are a worldwide health concern. For some infections, a common feature is the intracellular residence of the pathogen and evasion of the host immune response. In the case of tuberculosis (TB), Mycobacterium tuberculosis evades clearance within macrophages through suppression of intracellular reactive oxygen and nitrogen species (ROS/RNS) and pro-inflammatory cytokines. We propose new nanoparticle designs for infectious diseases, functionalized with ligands able to modulate the cellular immune response and concurrently deliver drug. We have designed 1,3-β-glucan functionalized chitosan shell, poly(lactide)co-glycolide core nanoparticles to stimulate ROS/RNS, pro-inflammatory cytokine secretion, and delivery of rifampicin inside human alveolar like macrophages (ALM). Nanoparticles significantly enhanced ALM secretion of IL-12p70 (2.9-fold), TNF-α (16-fold) and INF-γ (23-fold) compared to controls over 24h, and doubled ROS/RNS generation over 6h. Nanoparticles could deliver 4-fold greater rifampicin into ALM compared to rifampicin solution. These results provide proof-of-concept of multimodal nanoparticles and support their further development. From the Clinical Editor In this paper, a new nanoparticle design is proposed to address hard to treat infectious diseases such as TB, through the use of nanoparticles functionalized with ligands that are able to concurrently modulate the cellular immune response and deliver a drug. The authors have designed 1,3-β-glucan functionalized chitosan shell - poly(lactide)co-glycolide core nanoparticles to stimulate reactive oxygen and nitrogen species production, pro-inflammatory cytokine secretion, and delivery of rifampicin inside human alveolar-like macrophages.

Having unique architectural features, cationic polymeric nanocapsules (NCs) with well-defined covalently stabilized biodegradable structures were generated as potentially universal and safe therapeutic nanocarriers. These NCs were synthesized from allyl-functionalized cationic polylactide (CPLA) by highly efficient UV-induced thiol-ene interfacial cross-linking in transparent miniemulsions. With tunable nanoscopic sizes, negligible cytotoxicity and remarkable degradability, they are able to encapsulate doxorubicin (Dox) with inner cavities and bind interleukin-8 (IL-8) small interfering RNA (siRNA) with cationic shells. The Dox-encapsulated NCs can effectively bypass the P-glycoprotein (Pgp)-mediated multidrug resistance of MCF7/ADR cancer cells, thereby resulting in increased intracellular drug concentration and reduced cell viability. In vitro studies also showed that the NCs loaded with Dox, IL-8 siRNA and both agents can be readily taken up by PC3 prostate cancer cells, resulting in a significant chemotherapeutic effect and/or IL-8 gene silencing.

Pancreatic cancer is one of the deadliest cancers throughout the world with rarely efficient therapies currently available. Gene therapy on pancreatic cancer through small interfering RNA (siRNA)-based RNA interference (RNAi) has shown great potential and attracted much attention. However, due to the fragile nature of nucleic acid, the application of RNAi as a safe and efficient carrier faces great challenges. In this contribution, a self-assembly regime, which is based on well-defined cationic polylactides (CPLAs) with tertiary amine groups, has been used to encapsulate and protect siRNAs from fast degradation. CPLA is a safe and degradable formulation that allowed us to deliver siRNAs targeting the proangiogenic chemokine interleukin-8 (IL-8) to pancreatic cancer cells for gene therapy. Stable IL-8 siRNA-CPLA nanoplexes were successfully formed by electrostatic force and high gene transfection efficiencies were shown on two pancreatic cancer cell lines. We did not observe any cytotoxicity from these CPLAs over a large concentration range via cell viability evaluations. More importantly, the silencing of IL-8 gene expression significantly attenuated the proliferation of pancreatic cancer cells. Our preliminary results support the future development of gene therapy that might provide an effective and safe treatment approach towards pancreatic cancer.

The design, synthesis, and supramolecular organization of a nanocomposite in which nanoscale excitonic interactions between quantum dots and the chiral polymer dramatically enhance the optical activity is reported. This material is highly suitable for application in the emerging field of chiral photonics.

We present a magnetoplasmonic nanoplatform combining gold nanorods (GNR) and iron-oxide nanoparticles within phospholipid-based polymeric nanomicelles (PGRFe). The gold nanorods exhibit plasmon resonance absorbance at near infrared wavelengths to enable photoacoustic imaging and photothermal therapy, while the Fe 3 O 4 nanoparticles enable magnetophoretic control of the nanoformulation. The fabricated nanoformulation can be directed and concentrated by an external magnetic field, which provides enhancement of a photoacoustic signal. Application of an external field also leads to enhanced uptake of the magnetoplasmonic formulation by cancer cells in vitro. Under laser irradiation at the wavelength of the GNR absorption peak, the PGRFe formulation efficiently generates plasmonic nanobubbles within cancer cells, as visualized by confocal microscopy, causing cell destruction. The combined magnetic and plasmonic functionalities of the nanoplatform enable magnetic field-directed, imaging-guided, enhanced photo-induced cancer therapy. From the Clinical Editor In this study, a nano-formulation of gold nanorods and iron oxide nanoparticles is presented using a phospholipid micelle-based delivery system for magnetic field-directed and imaging-guided photo-induced cancer therapy. The gold nanorods enable photoacoustic imaging and photothermal therapy, while the Fe 3 O 4 nanoparticles enable magnetophoretic control of the formulation. This and similar systems could enable more precise and efficient cancer therapy, hopefully in the near future, after additional testing.

In this paper, a new method for synthesizing non-aqueous copper sulfide nanocrystals with different shapes and sizes using a homemade continuous-flow millifluidic chip is presented. Conventionally, the shape control of nanocrystals was accomplished using a surfactant-controlled approach, where directional growth is facilitated by selective passivation of a particular facet of the nanocrystals using surfactants. We demonstrate a "surfactant-free" approach where different sizes and shapes (i.e. spherical, triangular prism and rod) of plasmonic copper sulfide (Cu(2-x)S) nanocrystals can be fabricated by adjusting the flow rate and precursor concentrations. As continuous-flow synthesis enables uniform heating and easy variation of precursors' stoichiometries, it serves as an excellent incubation platform for nanoparticles due to its simplicity and high reproducibility. Transmission electron microscopy (TEM), fast Fourier transform (FFT) and X-ray diffraction (XRD) techniques were used to characterize the as-synthesized nanocrystals and revealed structures ranging from copper-deficient covellite (CuS), spionkopite (Cu1.39S), roxbyite (Cu1.75S), to copper-rich djurleite (Cu1.94S). The localized surface plasmon resonance (LSPR) peak of the nanocrystals can be tuned from 1115 to 1644 nm by simply varying the copper to sulfur molar ratio and flow rate. Furthermore, photothermal effects of Cu(2-x)S nanocrystals were also demonstrated to annihilate the RAW264.7 cells upon near infra-red laser irradiation.

Quantum dots have been used in biomedical research for imaging1,2, diagnostics3,4 and sensing purposes5,6. However, concerns over the cytotoxicity of their heavy metal constituents7,8 and conflicting results from in vitro7,9 and small animal10,11,12,13,14 toxicity studies have limited their translation towards clinical applications. Here, we show in a pilot study that rhesus macaques injected with phospholipid micelle-encapsulated CdSe/CdS/ZnS quantum dots do not exhibit evidence of toxicity. Blood and biochemical markers remained within normal ranges following treatment, and histology of major organs after 90 days showed no abnormalities. Our results show that acute toxicity of these quantum dots in vivo can be minimal. However, chemical analysis revealed that most of the initial dose of cadmium remained in the liver, spleen and kidneys after 90 days. This means that the breakdown and clearance of quantum dots is quite slow, suggesting that longer-term studies will be required to determine the ultimate fate of these heavy metals and the impact of their persistence in primates. Six rhesus macaques injected with a cadmium-based quantum-dot formulation survived without any evidence of toxicity, but cadmium remained in certain organs after 90 days.

We have synthesized core/shell NaGdF(4):Nd(3+)/NaGdF(4) nanocrystals with an average size of 15 nm and exceptionally high photoluminescence (PL) quantum yield. When excited at 740 nm, the nanocrystals manifest spectrally distinguished, near-infrared to near-infrared (NIR-to-NIR) downconversion PL peaked at ∼900, ∼1050, and ∼1300 nm. The absolute quantum yield of NIR-to-NIR PL reached 40% for core-shell nanoparticles dispersed in hexane. Time-resolved PL measurements revealed that this high quantum yield was achieved through suppression of nonradiative recombination originating from surface states and cross relaxations between dopants. NaGdF(4):Nd(3+)/NaGdF(4) nanocrystals, synthesized in organic media, were further converted to be water-dispersible by eliminating the capping ligand of oleic acid. NIR-to-NIR PL bioimaging was demonstrated both in vitro and in vivo through visualization of the NIR-to-NIR PL at ∼900 nm under incoherent lamp light excitation. The fact that both excitation and the PL of these nanocrystals are in the biological window of optical transparency, combined with their high quantum efficiency, spectral sharpness, and photostability, makes these nanocrystals extremely promising as optical biomaging probes.

Quantum dots (QDs) have size-dependent optical properties that make them uniquely advantageous for in vivo targeted fluorescence imaging, traceable delivery, and therapy. The use of group II-VI (e.g., CdSe) QDs for these applications is advancing rapidly. However, group II-VI QDs contain toxic heavy metals that limit their in vivo applications. Thus, replacing these with QDs of a biocompatible semiconductor, such as silicon (Si), is desirable. Here, we demonstrate that properly encapsulated biocompatible Si QDs can be used in multiple cancer-related in vivo applications, including tumor vasculature targeting, sentinel lymph node mapping, and multicolor NIR imaging in live mice. This work overcomes dispersibility and functionalization challenges to in vivo imaging with Si QDs through a unique nanoparticle synthesis, surface functionalization, PEGylated micelle encapsulation, and bioconjugation process that produces bright, targeted nanospheres with stable luminescence and long (>40 h) tumor accumulation time in vivo. Upon the basis of this demonstration, we anticipate that Si QDs can play an important role in more sophisticated in vivo models, by alleviating QD toxicity concerns while maintaining the key advantages of QD-based imaging methods.

Quantum dots (QDs), semiconductor nanocrystalssmall enough to exhibit size-dependent properties,have generated tremendous interest due to their un-ique optical properties [1–5], including broad excita-tion spectra [6], narrow, tunable [7] and symmetricemission spectra, and excellent photostability [8–14].Also, QDs are highly efficient multi-photon absor-bers that can be potentially useful for three dimen-sional multi-photon microscopy and imaging [15],which is a rapidly developing area for both biolo-gical and medical applications [16–19]. More impor-tantly, surface modification of QDs can be appliedto conjugate biomolecules (e.g. DNA, antibodies orproteins) to the QD surface to achieve selective tar-geting [20–23]. For instance, bioconjugated QDshave been used in cell labeling, tissue imaging,photosensitization for photodynamic therapy, in vivotumor detection, and drug delivery [24–27]. For the

Luminescent silicon quantum dots (SiQDs) are gaining momentum in bioimaging applications, based on their unique combination of optical properties and biocompatibility. Here, we report the development of a multimodal probe that combines the optical properties of silicon quantum dots with the superparamagnetic properties of iron oxide nanoparticles to create biocompatible magnetofluorescent nanoprobes. Multiple nanoparticles of each type are coencapsulated within the hydrophobic core of biocompatible phospholipid-polyethyleneglycol (DSPE-PEG) micelles. The size distribution and composition of the magnetofluorescent nanoprobes were characterized by transmission electron microscopy (TEM) and energy-dispersive X-ray spectroscopy (EDS). Enhanced cellular uptake of these probes in the presence of a magnetic field was demonstrated in vitro. Their luminescence stability in a prostate cancer tumor model microenvironment was demonstrated in vivo. This paves the way for multimodal silicon quantum-dot-based nanoplatforms for a variety of imaging and delivery applications.

Using the 3(rd) generation Grubbs' catalyst as the initiator, diblock brush polymer drug conjugates (BPDCs) were synthesized by sequential ring-opening metathesis polymerization (ROMP) of a hydrophilic poly(ethylene glycol) (PEG)-based norbornene (NB)-functionalized macromonomer and a hydrophobic paclitaxel (PTXL)-based NB-functionalized monomer. These amphiphilic diblock BPDCs had well-defined structures, with narrow molecular weight distributions (Mw/Mn = 1.10-1.16). They self-assembled into multi-molecular nanostructures in aqueous solutions. Although the PTXL moieties were connected to the backbone with cycloacetal-based conjugation linkages, the cleavage of these linkages from the assemblies of diblock BPDCs was relatively slow and exhibited limited acid-sensitivity, indicating a significant influence of the macromolecular structure and assembly of BPDCs on their drug release behaviour. The cytotoxicity study not only showed that the diblock BPDCs are therapeutically effective against cancer cells, but also revealed a correlation between cytotoxicity and grafting structures of BPDCs. In summary, the results obtained in this work provide new insight into the structure-dependent properties of brush polymer-based drug delivery systems.

Well-defined chitosan nanocapsules (CSNCs) with tunable sizes were synthesized through the interfacial cross-linking of N-maleoyl-functionalized chitosan (MCS) in miniemulsions, and their application in the delivery of doxorubicin (Dox) was investigated. MCS was prepared by the amidation reaction of CS with maleic anhydride in water/DMSO at 65 °C for 20 h. Subsequently, thiol-ene cross-linking was conducted in oil-in-water miniemulsions at room temperature under UV irradiation for 1 h, using MCS as both a surfactant and precursor polymer, 1,4-butanediol bis(3-mercapto-propionate) as a cross-linker, and D-α-tocopheryl poly(ethylene glycol) 1000 succinate as a cosurfactant. With the increase in cosurfactant concentration in the reaction systems, the sizes of the resulting CSNCs decreased steadily. Dox-loaded CSNCs were readily prepared by in situ encapsulation of Dox during miniemulsion cross-linking. With acid-labile β-thiopropionate cross-linkages, the Dox-loaded CSNCs demonstrated a faster release rate under acidic conditions. Relative to free Dox, Dox-loaded CSNCs exhibited enhanced cytotoxicity toward MCF-7 breast cancer cells without any noticeable cytotoxicity from empty CSNCs. The effective delivery of Dox to MCF-7 breast cancer cells via Dox-loaded CSNCs was also observed.

Bionanocombinatorics is an emerging field that aims to use combinations of positionally encoded biomolecules and nanostructures to create materials and devices with unique properties or functions. The full potential of this new paradigm could be accessed by exploiting specific noncovalent interactions between diverse palettes of biomolecules and inorganic nanostructures. Advancement of this paradigm requires peptide sequences with desired binding characteristics that can be rationally designed, based upon fundamental, molecular-level understanding of biomolecule-inorganic nanoparticle interactions. Here, we introduce an integrated method for building this understanding using experimental measurements and advanced molecular simulation of the binding of peptide sequences to gold surfaces. From this integrated approach, the importance of entropically driven binding is quantitatively demonstrated, and the first design rules for creating both enthalpically and entropically driven nanomaterial-binding peptide sequences are developed. The approach presented here for gold is now being expanded in our laboratories to a range of inorganic nanomaterials and represents a key step toward establishing a bionanocombinatorics assembly paradigm based on noncovalent peptide-materials recognition.

We report a new type of heterogeneous nanoparticles (NPs) composed of a heavily doped semiconductor domain (Cu2–xSe) and a metal domain (Au), which exhibit a broad localized surface plasmon resonance (LSPR) across visible and near-infrared (NIR) wavelengths, arising from interactions between the two nanocrystal domains. We demonstrate both in vivo photoacoustic imaging and in vitro dark field imaging, using the broad LSPR in Cu2–xSe–Au hybrid NPs to achieve contrast at different wavelengths. The high photoacoustic imaging depth achieved, up to 17 mm, shows that these novel contrast agents could be clinically relevant. More broadly, this work demonstrates a new strategy for tuning LSPR absorbance by engineering the density of free charge carriers in two interacting domains.

Luminescent imaging agents and MRI contrast agents are desirable components in the rational design of multifunctional nanoconstructs for biological imaging applications. Luminescent biocompatible silicon quantum dots (SiQDs) and gadolinium chelates can be applied for fluorescence microscopy and MRI, respectively. Here, we report the first synthesis of a nanocomplex incorporating SiQDs and gadolinium ions (Gd3+) for biological applications. The nanoconstruct is composed of a PEGylated micelle, with hydrophobic SiQDs in its core, covalently bound to DOTA-chelated Gd3+. Dynamic light scattering reveals a radius of 85 nm for these nanoconstructs, which is consistent with the electron microscopy results depicting radii ranging from 25 to 60 nm. Cellular uptake of the probes verified that they maintain their optical properties within the intracellular environment. The magnetic resonance relaxivity of the nanoconstruct was 2.4 mM−1 s−1 (in terms of Gd3+ concentration), calculated to be around 6000 mM−1 s−1 per nanoconstruct. These desirable optical and relaxivity properties of the newly developed probe open the door for use of SiQDs in future multimodal applications such as tumour imaging.

The application of small interfering RNA (siRNA)-based RNA interference (RNAi) for cancer gene therapy has attracted great attention. Gene therapy is a promising strategy for cancer treatment because it is relatively non-invasive and has a higher therapeutic specificity than chemotherapy. However, without the use of safe and efficient carriers, siRNAs cannot effectively penetrate the cell membranes and RNAi is impeded. In this work, cationic poly(lactic acid) (CPLA)-based degradable nanocapsules (NCs) are utilized as novel carriers of siRNA for effective gene silencing of pancreatic cancer cells. These CPLA-NCs can readily form nanoplexes with K-Ras siRNA and over 90% transfection efficiency is achieved using the nanoplexes. Cell viability studies show that the nanoparticles are highly biocompatible and non-toxic, indicating that CPLA-NC is a promising potential candidate for gene therapy in a clinical setting.

In this paper, we report on the enhancement of spectral photoresponsivity of porous silicon metal–semiconductor metal (PS-MSM) photodetector embedded with colloidal quantum dots (QDs) inside the pore layer. The detection efficiency of QDs/PS hybrid-MSM photodetector was enhanced by five times larger than that of the undoped PS-MSM photodetector. The bandgap alignment between PS (approximately 1.77 eV) and QDs (approximately 1.91 eV) facilitates the photoinduced electron transfer from QDs to PS whereby enhancing the photoresponsivity. We also showed that the photoresponsitivity of QD/PS hybrid-MSM photodetector depends on the number of layer coatings of QDs and the pore sizes of PS.

In this study, we report the development of a nanoparticle-enhanced biosensor by integrating both the nanoparticles and immunoassay sensing technologies into a phase interrogation surface plasmon resonance (SPR) system for detecting antigen at a concentration as low as the femtomolar range. Our work has demonstrated that the plasmonic field extension generated from the gold film to gold nanorod (GNR) has led to a drastic sensitivity enhancement. Antibody-functionalized sensing film, together with antibody-conjugated GNRs, was readily served as a plasmonic coupling partner that can be used as a powerful ultrasensitive sandwich immunoassay for cancer-related disease detection. Experimentally, it was found that the bioconjugated GNR labels enhance the tumor necrosis factor alpha (TNF-α) antigen signal with more than 40-fold increase compared to the traditional SPR biosensing technique. The underlying principle was analyzed by simulating the near-field coupling between the sensing film and the GNR. The results have shown that GNRs were readily served as promising amplification labels in SPR sensing technology.

In this study, we have developed a novel carrier, micelle-type bioconjugated PLGA-4-arm-PEG branched polymeric nanoparticles (NPs), for the detection and treatment of pancreatic cancer. These NPs contained 4-arm-PEG as corona, and PLGA as core, the particle surface was conjugated with cyclo(arginine-glycine-aspartate) (cRGD) as ligand for in vivo tumor targeting. The hydrodynamic size of the NPs was determined to be 150-180 nm and the critical micellar concentration (CMC) was estimated to be 10.5 mg l( - 1). Our in vitro study shows that these NPs by themselves had negligible cytotoxicity to human pancreatic cancer (Panc-1) and human glioblastoma (U87) cell lines. Near infrared (NIR) microscopy and flow cytometry demonstrated that the cRGD conjugated PLGA-4-arm-PEG polymeric NPs were taken up more efficiently by U87MG glioma cells, over-expressing the α(v)β(3) integrin, when compared with the non-targeted NPs. Whole body imaging showed that the cRGD conjugated PLGA-4-arm-PEG branched polymeric NPs had the highest accumulation in the pancreatic tumor site of mice at 48 h post-injection. Physical, hematological, and pathological assays indicated low in vivo toxicity of this NP formulation. These studies on the ability of these bioconjugated PLGA-4-arm-PEG polymeric NPs suggest that the prepared polymeric NPs may serve as a promising platform for detection and targeted drug delivery for pancreatic cancer.

We report core/shell NaYbF(4):Tm(3+)/NaGdF(4) nanocrystals to be used as probes for bimodal near infrared to near infrared (NIR-to-NIR) upconversion photoluminescence (UCPL) and magnetic resonance (MR) imaging. The NaYbF(4):Tm(3+) nanocrystals were previously reported to produce the intense NIR-to-NIR UCPL peaked at ∼800 nm under excitation at ∼975 nm. We have found that the growth of a NaGdF(4) shell on surface of the NaYbF(4):Tm(3+) nanocrystals results in the increase in the intensity of UCPL of Tm(3+) ions by about 3 times. Unlike biexponential PL decay of NaYbF(4):Tm(3+) nanocrystals, the PL decay of NaYbF(4):Tm(3+)/NaGdF(4) core/shell nanocrystals is single exponential and of longer lifetime due to the suppression of surface quenching effects for Tm(3+) PL. The growth of a NaGdF(4) shell on surface of the NaYbF(4):Tm(3+) nanocrystals also provides high MR relaxivity from paramagnetic Gd(3+) ions contained in the shell. The T1-weighted MR signal of the (NaYbF(4):2% Tm(3+))/NaGdF(4) nanoparticles was measured to be about 2.6 mM(-1)s(-1). Due to the combined presence of efficient optical and MR imaging capabilities, nanoprobes based on NaYbF(4):Tm(3+)/NaGdF(4) fluoride nanophosphors can be considered as a promising platform for simultaneous bimodal PL and MR bioimaging.

In this study QDs were encapsulated in carboxylated PluronicF127 (F127COOH) triblock polymeric micelles and conjugated with anti-mesothelin antibody for the purpose of alleviating potential toxicity, enhancing the stability and improving targeting efficiency of CdTe/ZnS quantum dots (QDs) in tumors. The amphiphilic triblock polymer of F127COOH contains hydrophilic carboxylated poly(ethylene oxide) (PEO) and hydrophobic poly(propylene oxide) (PPO) units. After encapsulating QDs into carboxylated F127 (F127COOH-QD) micelles, the particles were conjugated with anti-mesothelin antibodies to allow targeting of cancerous areas. The size of the monodispersed spherical QD-containing micelles was determined to be ∼120 nm by dynamic light scattering (DLS). The critical micelle concentration (CMC) was estimated to be 4.7 × 10(-7) M. In an in vitro study, the anti-methoselin antibody conjugated F127COOH (Me-F127COOH-QD) nanomicelles showed negligible cytotoxicity to pancreatic cancer cells (Panc-1). Confocal microscopy demonstrated that the Me-F127COOH-QD nanomicelles were taken up more efficiently by Panc-1 cells, due to antibody mediated targeting. An in vivo imaging study showed that Me-F127COOH-QD nanomicelles accumulated at the pancreatic tumor site 15 min after intravenous injection. In addition, the low in vivo toxicity of the nanomicellar formulation was evaluated by pathological assays. These results suggest that anti-mesothein antibody conjugated carboxylated F127 nanomicelles may serve as a promising nanoscale platform for early human pancreatic cancer detection and targeted drug delivery.

In this paper, we report the use of near-infrared (NIR)-emitting alloyed quantum dots (QDs) as efficient optical probes for high contrast in vivo imaging of tumors. Alloyed CdTe(1 - x)Se(x)/CdS QDs were prepared in the non-aqueous phase using the hot colloidal synthesis approach. Water dispersion of the QDs were accomplished by their encapsulation within polyethyleneglycol (PEG)-grafted phospholipid micelles. For tumor-specific delivery in vivo, the micelle-encapsulated QDs were conjugated with the cyclic arginine-glycine-aspartic acid (cRGD) peptide, which targets the alpha(v)beta(3) integrins overexpressed in the angiogenic tumor vasculatures. Using in vivo NIR optical imaging of mice bearing pancreatic cancer xenografts, implanted both subcutaneously and orthotopically, we have demonstrated that systemically delivered cRGD-conjugated QDs, but not the unconjugated ones, can efficiently target and label the tumors with high signal-to-noise ratio. Histopathological analysis of major organs of the treated mice showed no evidence of systemic toxicity associated with these QDs. These experiments suggest that cRGD-conjugated NIR QDs can serve as safe and efficient probes for optical bioimaging of tumors in vivo. Furthermore, by co-encapsulating these QDs and anticancer drugs within these micelles, we have demonstrated a promising theranostic, nanosized platform for both cancer imaging and therapy.

The ability to provide targeted therapeutic delivery in the lung would be a major advancement in pharmacological treatments for many pulmonary diseases. Critical issues for such successful delivery would require the ability to target specific cell types, minimize toxicity (e.g., inflammatory response), and deliver therapeutic levels of drugs. We report here on the ability of nanoconjugates of CdSe/CdS/ZnS quantum dots (QDs) and doxorubicin (Dox) to target alveolar macrophages (aMØs), cells that play a critical role in the pathogenesis of inflammatory lung injuries. Confocal imaging showed the release of Dox from the QD-Dox nanoconjugate, as was evident by its accumulation in the cell nucleus and induction of apoptosis, implying that the drug retains its bioactivity after coupling to the nanoparticle. Inflammatory injury parameters (albumin leakage, proinflammatory cytokines, and neutrophil infiltration) were recorded after in vivo administration of QD-Dox and Dox, observing no significant effect after QD-Dox treatment compared with Dox. These results demonstrate that nanoparticle platforms can provide targeted macrophage-selective therapy for the treatment of pulmonary disease.Pulmonary inflammatory diseases still often remain challenging to treat, despite decades of advances and several available agents. In this study, a quantum dot-based alveolar delivery system is presented, targeting macrophages with doxorubicin.

In this paper, we report the successful use of non-cadmium based quantum dots (QDs) as highly efficient and non-toxic optical probes for imaging live pancreatic cancer cells. Indium phosphide (core)-zinc sulphide (shell), or InP/ZnS, QDs with high quality and bright luminescence were prepared by a hot colloidal synthesis method in non-aqueous media. The surfaces of these QDs were then functionalized with mercaptosuccinic acid to make them highly dispersible in aqueous media. Further bioconjugation with pancreatic cancer specific monoclonal antibodies, such as anti-claudin 4 and anti-prostate stem cell antigen (anti-PSCA), to the functionalized InP/ZnS QDs, allowed specific in vitro targeting of pancreatic cancer cell lines (both immortalized and low passage ones). The receptor mediated delivery of the bioconjugates was further confirmed by the observation of poor in vitro targeting in non-pancreatic cancer based cell lines which are negative for the claudin-4-receptor. These observations suggest the immense potential of InP/ZnS QDs as non-cadmium based safe and efficient optical imaging nanoprobes in diagnostic imaging, particularly for early detection of cancer.

Semiconductor quantum dots (QDs) have traditionally been synthesized in organic phase and transferred to aqueous solution by functionalizing their surface with silica, polymers, short-chain thiol ligand, or phospholipid micelles. However, these complex steps result in i) a reduction of the quantum yield (QY) of QDs, ii) partial degrdation of the QDs, and iii) a drastic increase in the hydrodynamic size of QDs, which may hinder their biomedical applications. In this work, the fabrication and applications of cysteine-capped CdTe/ZnTe QDs, which are directly synthesized in aqueous media, as optical probes for specific targeting of pancreatic and esophageal cancer cells in vitro are reported, as well as their capability for in vivo imaging. The CdTe/ZnTe QDs are synthesized in a one-pot method and capped with amino acid cysteine, which contains both carboxyl and amine functional groups on their surfaces for bioconjugation. The fabricated QDs have an ultrasmall hydrodynamic diameter (3-5 nm), possess high QY (52%), and are non-toxic to cells at experimental dosages. Confocal imaging is used to demonstrate a receptor-mediated uptake of antibody-conjugated QDs into pancreatic cancer cells in vitro. In vitro cytotoxicity studies (MTS-assay) show that the IC(50) value of these QDs is approximately 160 microg mL(-1), demonstrating low toxicity. In addition, the QDs are used for small-animal imaging where the in vivo biocompatiblity of these QDs and their clearance following systemic injection is studied.