Hybrid nanostructures with combined functionalities can be rationally designed to achieve synergistic effects for efficient cancer treatment. Herein, a multifunctional nanoplatform is constructed, containing an inner core of an anticancer drug MTX surrounding by a nanometer-thin layer of gold as the shell with Fe3O4 magnetic nanoparticles (NPs) evenly distributed in the gold layer, and the outermost hybrid LA-PEG-MTX molecules as surface coating agent (denoted as MFG-LPM NPs). This nanocomposite possesses very high drug loading capacity as the entire core is MTX and integrates magnetic- and active- targeting drug delivery, light-controlled drug release, magnetic resonance imaging (MRI), as well as photothermal and chemotherapy. With a strong near-infrared (NIR) absorbance at 808 nm, the nanocomposite enables temperature elevation and light-triggered MTX release. In vitro cytotoxicity studies indicate that the strategy of combining therapy leads to a synergistic effect with high cancer cell killing efficacy. In consistency with this, due to the high accumulation of MFG-LPM NPs at tumor site and their combinatorial chemo-photothermal effects, 100% in vivo tumor elimination can be achieved. Additionally, in vivo MRI of tumor-bearing mice demonstrates an impressive performance of MFG-LPM NPs as a T2 contrast agent. Therefore, such multifunctional nanocomposite has the potential to serve as an excellent theranostic agent that collectively integrates multiple functions for efficient MRI guided cancer diagnosis and treatment.Keywords: chemotherapy; dual-target; magnetic resonance imaging; multifunctional nanocomposite; photothermal;

Thermally activated delayed fluorescence (TADF) emitters have attracted much interest for their great applications in organic light-emitting diodes (OLEDs), but the TADF OLEDs are limited by large efficiency roll-offs. In this study, we report two coumarin-based TADF emitters, 3-methyl-6-(10H-phenoxazin-10-yl)-1H-isochromen-1-one (PHzMCO) and 9-(10H-phenoxazin-10-yl)-6H-benzo[c]chromen-6-one (PHzBCO), with relatively high photoluminescence quantum yields (PLQYs) and extremely small singlet–triplet splittings. OLEDs using these two TADF compounds as the emitters respectively demonstrate high external quantum efficiencies of 17.8% for PHzMCO and 19.6% for PHzBCO, which are the highest among the reported coumarin-derivative-based OLEDs. More importantly, these devices based on PHzMCO and PHzBCO remained 10.3% and 12.9% at 10000 cd m–2, respectively, showing relatively low efficiency roll-offs at high brightness. These results reveal that the TADF emitters with high PLQYs can effectively reduce the efficiency roll-off in the devices.Keywords: coumarin derivatives; high external quantum efficiency; low efficiency roll-off; organic light-emitting diodes; thermally activated delayed fluorescence;

Lonidamine (LND) can act on mitochondria and inhibit energy metabolism in cancer cells and therefore has been used together with chemotherapy drugs for synergistically enhanced therapeutic efficacy. However, its use is hindered by the poor solubility and slow diffusion in the cytoplasm. To address these problems, we designed and prepared aqueous dispersible nanoparticles (NPs) containing integrated components including triphenylphosphine (TPP) to target the mitochondria of cells and LND and doxorubicin (DOX) for synergistic cancer treatment and conquering drug resistance. This design allows the NPs to concentrate in the mitochondria of cells, solve the low solubility of LND, and contain very high load of LND and DOX in comparison with previously reported drug-delivery systems based on various carrier nanomaterials. Detailed mechanism studies reveal that TPP-LND-DOX NPs could induce significant reactive oxygen species production, mitochondrial membrane potential decrease, and mitochondrial apoptosis pathway, thereby leading to great cytotoxicity in cancer cells. In vivo anticancer activities indicate that TPP-LND-DOX NPs exhibit the highest efficacy in tumor inhibition among all tested groups and show high effectiveness in drug-resistant model. This work demonstrates the potential use of our TPP-LND-DOX NPs to jointly promote the mitochondria apoptosis pathway and contribute to conquer drug resistance in cancer therapy.Keywords: chemotherapy; drug resistance; lonidamine; mitochondria targeting; triphenylphosphine;

We report a general and robust polymerization–dissolution strategy for phase transfer of hydrophilic nanoparticles into nonaqueous solvents with a 100% transfer efficiency. This process involves the coating of hydrophilic nanoparticles with a layer of linear-chained polystyrene through seeded emulsion polymerization and a subsequent dissolution of polystyrene layer by toluene. Since one end of the linear polystyrene chain is covalently bonded to the particle surface which provides strong steric stabilization, the transferred nanoparticles exhibit superior dispersity and long-term colloidal stability in many nonpolar and polar aprotic solvents. Moreover, the present approach allows for the storage of transferred nanoparticles in a powder form which can be completely re-dispersed in solvents before the usage. Based on this strategy, we demonstrate the phase transfer of Au nanorods and nanospheres, silica, titania and resorcinol-formaldehyde spheres, which just represents a few examples of transferrable hydrophilic nanoparticles with different morphologies, sizes, compositions, functions and surface properties. This general and robust phase transfer protocol will greatly facilitate the applications of hydrophilic nanoparticle in organic catalysis, optoelectronics, energy storage and conversion, and organic light emitting diodes.

•GQDs/Si heterojunctions were constructed via a simple drop-casting method.•Graphene layer was adopted as transparent electrode to ensure the efficient light absorption and carrier transportation.•A recorded high power conversion efficiency (PCE) of 12.35% was achieved.Zero-dimensional graphene quantum dots (GQDs) have lately intrigued intensive interest because of their great promise in energy, optoelectronic, and bio-imaging applications. Herein, we demonstrated the fabrication of highly efficient GQDs/n-silicon heterojunction solar cells via a simple solution process. Owing to the unique band structure, the GQDs layer could not only serve as hole transport layer to facilitate the separation of photo-generated electron-hole pairs, but also act as electron blocking layer to suppress the carrier recombination at anode. Moreover, graphene was used as the transparent top electrode for the heterojunction solar cells, ensuring the efficient light absorption and carrier collection. By adjusting the sizes of GQDs and the thickness of GQDs layer, a power conversion efficiency (PCE) as high as 12.35% under AM 1.5G irradiation was achieved, which represented a new efficiency record for this new-type solar cell. The devices also exhibited excellent stability in air due to the high chemical/physical stability of GQDs and graphene. The successful achievement of the high-efficiency GQDs/Si heterojunction solar cells opens up the opportunities for their potential applications in high-performance and low-cost photovoltaics.

Graphene/silicon heterojunction solar cells have stimulated enormous research interests due to simple device architecture and low-cost solution-processing capability. Graphene can serve as p-type layer to form heterojunction with n-type crystalline Si. However, improvement of device performance is hindered by the relatively low junction height arising from the small work function of graphene. Herein, for the first time, we develop and implement a surface inversion layer on Si substrates by surface charge transfer doping (SCTD) scheme using a layer of high work function metal oxide (MoO3) as a hole injection layer on Si surface. Spontaneous hole injection from the MoO3 layer to Si led to the generation of a hole inversion layer on Si surface, greatly enhancing the built-in electric potential and suppressing the carrier recombination. The use of SCTD method, in combination with additional device optimization by graphene doping and polymer anti-reflection coating, results in a high power conversion efficiency approaching 12.2%. The SCTD scheme provides a new platform to further enhance the performance of graphene/silicon heterojunction solar cells.

•Surface engineering of dye nanoparticles can dramatically induce over ten-fold enhancement in bioimaging brightness.•Specific non-clathrin- and non-caveolae-mediated pathway is observed.•Enhanced cellular uptake efficacy and decreased cellular excretion endow dye nanoparticles with superior bioimaging performance.Surface properties of nanoparticles (NPs) have a huge influence on their biological activities. In this work, we report to use mesoporous silica nanoshell surface to regulate the cellular internalization rate and intracellular fate of fluorescent organic NPs for highly improved cellular imaging. We systematically studied the internalization of the NPs into cells, the intracellular transport pathways, the excretion from cells, and very importantly, compared the results with those from various NPs with different surface properties. It was found that the silica nanoshell coating allow the NPs to achieve strikingly improved brightness in imaging (over ten-fold enhancement) and much higher delivery efficiency than other NPs. This was attributed to their unique non-clathrin- and non-caveolae-mediated pathways which enable them to enter cells very efficiently and quickly in the cellular internalization, as well as their low cellular excretion rate. This highly effective cellular imaging effect caused by silica surface coating is much desirable for applications in sensitive imaging and long-term tracking of cells.Download high-res image (175KB)Download full-size image

Many drug molecules can be directly used as nanomedicine without the requirement of any inorganic or organic carriers such as silica and liposome nanostructures. This new type of carrier-free drug nanoparticles (NPs) has great potential in clinical treatment because of its ultra-high drug loading capacity and biodegradability. For practical applications, it is essential for such nanomedicine to possess robust stability and minimal premature release of therapeutic molecules during circulation in the blood stream. To meet this requirement, herein, we develop GSH-responsive and crosslinkable amphiphilic polyethylene glycol (PEG) molecules to modify carrier-free drug NPs. These PEG molecules can be cross-linked on the surface of the NPs to endow them with greater stability and the cross-link is sensitive to intracellular environment for bio-responsive drug release. With this elegant design, our experimental results show that the liberation of DOX from DOX-cross-linked PEG NPs is dramatically slower than that from DOX-non-cross-linked PEG NPs, and the DOX release profile can be controlled by tuning the concentration of the reducing agent to break the cross-link between PEG molecules. More importantly, in vivo studies reveal that the DOX-cross-linked PEG NPs exhibit favorable blood circulation half-life (>4 h) and intense accumulation in tumor areas, enabling effective anti-cancer therapy. We expect this work will provide a powerful strategy for stabilizing carrier-free nanomedicines and pave the way to their successful clinical applications in the future.

In this study, we report fluorescent organic nanoprobes with intense blue, green, and orange-red emissions prepared by self-assembling three carbazole derivatives into nanorods/nanoparticles. The three compounds consist of two or four electron-donating carbazole groups linked to a central dicyanobenzene electron acceptor. Steric hindrance from the carbazole groups leads to noncoplanar 3D molecular structures favorable to fluorescence in the solid state, while the donor–acceptor structures endow the molecules with good two-photon excited emission properties. The fluorescent organic nanoprobes exhibit good water dispersibility, low cytotoxicity, superior resistance against photodegradation and photobleaching. Both one- and two-photon fluorescent imaging were shown in the A549 cell line. Two-photon fluorescence imaging with the fluorescent probes was demonstrated to be more effective in visualizing and distinguishing cellular details compared to conventional one-photon fluorescence imaging.Keywords: carbazole derivatives; electron donor−acceptor; fluorescent organic nanoprobes; self-assembly; two-photon cellular imaging

Causes of efficiency limitation in common fluorescence and phosphorescence hybrid white organic light-emitting devices (WOLEDs) are discussed, and a new device architecture is proposed to address these issues. This architecture employs a fluorescent emitting layer (EML) of blue exciplex-forming cohost, which shows broad and strong thermally activated delayed fluorescence (TADF). Hybrid WOLEDs based on this architecture not only allow complete triplet harvesting for light generation but also can achieve white light emission with high color rending indexes (CRI) using only two colors. By using 26DCzPPy:PO-T2T as the blue fluorescent EML and 26DCzPPy:Ir complexes as the phosphorescent EML, we prepared a series of two-color WOLEDs with low turn-on voltages of 2.5–3.3 V, high forward-viewing EQEs of 12.7–19.3% and high CRIs of 67–77. These results suggest this new architecture would be an effective way to achieve high performance WOLEDs with simple structures.Keywords: delayed fluorescence; exciplex; hybrid WOLED; phosphor; triplet harvest

Pure nanodrugs (PNDs), nanoparticles consisting entirely of drug molecules, have been considered as promising candidates for next-generation nanodrugs. However, the traditional preparation method via reprecipitation faces critical challenges including low production rates, relatively large particle sizes, and batch-to-batch variations. Here, for the first time, we successfully developed a novel, versatile, and controllable strategy for preparing PNDs via an anodized aluminum oxide (AAO) template-assisted method. With this approach, we prepared PNDs of an anticancer drug (VM-26) with precisely controlled sizes reaching the sub-20 nm range. This template-assisted approach has much higher feasibility for mass production comparing to the conventional reprecipitation method and is beneficial for future clinical translation. The present method is further demonstrated to be easily applicable for a wide range of hydrophobic biomolecules without the need of custom molecular modifications and can be extended for preparing all-in-one nanostructures with different functional agents.

Considering the obvious advantages in efficacy and price, doxorubicin (DOX) has been widely used for a range of cancers, which is usually encapsulated in various nanocarriers for drug delivery. Although effective, in most nanocarrier-based delivery systems, the drug loading capacity of DOX is rather low; this can lead to undesired systemic toxicity and excretion concern. Herein, we report for the first time the usage of pure doxorubicin nanoparticles (DOX NPs) without addition of any carriers for enhanced chemotherapy against drug-resistance. The drug payload reaches as high as 90.47%, which largely surpassed those in previous reports. These PEG stabilized DOX NPs exhibit good biocompatibility and stability, long blood circulation time, fast release in an acidic environment and high accumulation in tumors. Compared with free DOX, DOX NPs display a dramatically enhanced anticancer therapeutic efficacy in the inhibition of cell and tumor growth. Moreover, they can also be readily incorporated with other anticancer drugs for synergistic chemotherapy to overcome the drug resistance of cancers. The fluorescence properties of DOX also endow these NPs with imaging capabilities, thus making it a multifunctional system for diagnosis and treatment. This work demonstrates great potential of DOX NPs for cancer diagnosis, therapy and overcoming drug tolerance.

In this paper, we investigated the aspect ratio (AR) effect of anticancer drug nanocrystals (NCs) on their cellular internalization efficiency, uptake mechanisms, biodistributions as well as in vitro and in vivo antitumor efficiencies. Both confocal imaging and flow cytometry show that shorter NCs with AR = 1.3 have a much faster cellular uptake rate and a much higher anticancer efficacy than longer NCs. All NCs with different ARs were found to enter the cells via an energy-dependent clathrin-mediated pathway. In vivo experiments indicate that NCs with higher ARs have a shorter half-life and are more easily captured by the liver, while the corresponding tumor uptake decreased. We also observed that NCs with the smallest AR have the highest therapeutic efficacy with appreciably less weight loss. These results would assist in the future design of drug NCs and may lead to the development of new drug nanostructures for biomedical applications.

Theranostic nanomedicine is capable of diagnosis, therapy, and monitoring the delivery and distribution of drug molecules and has received growing interest. Herein, a self-monitored and self-delivered photosensitizer-doped FRET nanoparticle (NP) drug delivery system (DDS) is designed for this purpose. During preparation, a donor/acceptor pair of perylene and 5,10,15,20-tetro (4-pyridyl) porphyrin (H2TPyP) is co-doped into a chemotherapeutic anticancer drug curcumin (Cur) matrix. In the system, Cur works as a chemotherapeutic agent. In the meantime, the green fluorescence of Cur molecules is quenched (OFF) in the form of NPs and can be subsequently recovered (ON) upon release in tumor cells, which enables additional imaging and real-time self-monitoring capabilities. H2TPyP is employed as a photodynamic therapeutic drug, but it also emits efficient NIR fluorescence for diagnosis via FRET from perylene. By exploiting the emission characteristics of these two emitters, the combinatorial drugs provide a real-time dual-fluorescent imaging/tracking system in vitro and in vivo, and this has not been reported before in self-delivered DDS which simultaneously shows a high drug loading capacity (77.6%Cur). Overall, our carrier-free DDS is able to achieve chemotherapy (Cur), photodynamic therapy (H2TPyP), and real-time self-monitoring of the release and distribution of the nanomedicine (Cur and H2TPyP). More importantly, the as-prepared NPs show high cancer therapeutic efficiency both in vitro and in vivo. We expect that the present real-time self-monitored and self-delivered DDS with multiple-therapeutic and multiple-fluorescent ability will have broad applications in future cancer therapy.Keywords: combination therapy; FRET; in vitro; in vivo; self-delivery; self-monitoring;

Graphene/silicon heterojunction solar cells have stimulated enormous research interests due to simple device architecture and low-cost solution-processing capability. Graphene can serve as p-type layer to form heterojunction with n-type crystalline Si. However, improvement of device performance is hindered by the relatively low junction height arising from the small work function of graphene. Herein, for the first time, we develop and implement a surface inversion layer on Si substrates by surface charge transfer doping (SCTD) scheme using a layer of high work function metal oxide (MoO3) as a hole injection layer on Si surface. Spontaneous hole injection from the MoO3 layer to Si led to the generation of a hole inversion layer on Si surface, greatly enhancing the built-in electric potential and suppressing the carrier recombination. The use of SCTD method, in combination with additional device optimization by graphene doping and polymer anti-reflection coating, results in a high power conversion efficiency approaching 12.2%. The SCTD scheme provides a new platform to further enhance the performance of graphene/silicon heterojunction solar cells.