Photosensitizer and Autophagy Promoter Coloaded ROS‐Responsive Dendrimer‐Assembled Carrier for Synergistic Enhancement of Tumor Growth Suppression

Reactive oxygen species (ROS) generated during photodynamic therapy (PDT) can trigger autophagy. However, little research is focused on whether there is a synergistic anticancer effect with PDT if extra autophagy promoter or inhibitor is added. Here, it is found that autophagy promotion significantly enhances the PDT activity to cancer cells. Based on this preliminary result, a ROS‐sensitive self‐assembled dendrimer nanoparticle is exploited as a carrier to codeliver an autophagy promoter (rapamycin, Rapa) and photosensitizer (phthalocyanine, Pc) to the tumor. After entrapped by cancer cells and irradiated by light, the ROS generated in PDT process of Pc can trigger nanoparticle destruction to release Rapa, thus initiating the autophagy process and remarkably enhancing the efficacy of PDT, leading to efficient tumor suppression.     

Highly Efficient Photosensitizers with Far‐Red/Near‐Infrared Aggregation‐Induced Emission for In Vitro and In Vivo Cancer Theranostics

Fluorescence‐imaging‐guided photodynamic therapy has emerged as a promising protocol for cancer theranostics. However, facile preparation of such a theranostic material for simultaneously achieving bright emission with long wavelength, high‐performance reactive oxygen species (ROS) generation, and good targeting‐specificity of cancer cells, is highly desirable but remains challenging. In this study, a novel type of far‐red/near‐infrared‐emissive fluorescent molecules with aggregation‐induced emission (AIE) characteristics is synthesized through a few steps reaction. These AIE luminogens (AIEgens) possess simple structures, excellent photostabilities, large Stokes shifts, bright emission, and good biocompatibilities. Meanwhile, their ROS generation is extremely efficient with up to 90.7% of ROS quantum yield, which is far superior to that of some popularly used photosensitizers. Importantly, these AIEgens are able to selectively target and ablate cancer cells over normal cells without the aid of any extra targeting ligands. Rather than using laser light, one of the presented AIEgens (MeTTPy) shows a remarkable tumor‐targeting photodynamic therapeutic effect by using an ultralow‐power lamp light (18 mW cm^?2). This study thus not only extends the applications scope of AIEgens, but also offers useful insights into designing a new generation of cancer theranostics.     

Near‐Infrared Switchable Fullerene‐Based Synergy Therapy for Alzheimer's Disease

C₆₀ has a special dual function; it can act as both a powerful reactive oxygen species (ROS) producer under UV or visible light and an ROS scavenger in the dark. However, ROS has double‐edged effects in living systems. It is still a great challenge for biomedical application to switch and adjust the two opposite properties of C₆₀ in one system. Herein, UCNP@C₆₀‐pep (UCNP: upconversion nanoparticle, pep: Aβ‐target peptide KLVFF) is designed as a near‐infrared‐switchable nanoplatform for synergy therapy of Alzheimer's disease (AD). Under near‐infrared (NIR) light, the Aβ‐targeting hybrid nanoparticles produce ROS and result in Aβ photooxygenation, which can hinder Aβ aggregation and mitigate the attendant cytotoxicity. In the dark, UCNP@C₆₀‐pep shows protective effects against the increased oxidative stress. The ROS‐generating and ROS‐quenching abilities of UCNP@C₆₀‐pep are both beneficial for decreasing Aβ‐induced neurotoxicity and extending the longevity of the commonly used transgenic AD model Caenorhabditis elegans CL2006. Moreover, UCNP@C60‐pep can also be used for upconversion luminescence (UCL) and magnetic resonance imaging (MRI), which has benefits for “image‐guided therapy.” This study may offer a new perspective for the biological applications of C₆₀.     

Large‐Scale Direct‐Writing of Aligned Nanofibers for Flexible Electronics

Nanofibers/nanowires usually exhibit exceptionally low flexural rigidities and remarkable tolerance against mechanical bending, showing superior advantages in flexible electronics applications. Electrospinning is regarded as a powerful process for this 1D nanostructure; however, it can only be able to produce chaotic fibers that are incompatible with the well‐patterned microstructures in flexible electronics. Electro‐hydrodynamic (EHD) direct‐writing technology enables large‐scale deposition of highly aligned nanofibers in an additive, noncontact, real‐time adjustment, and individual control manner on rigid or flexible, planar or curved substrates, making it rather attractive in the fabrication of flexible electronics. In this Review, the ground‐breaking research progress in the field of EHD direct‐writing technology is summarized, including a brief chronology of EHD direct‐writing techniques, basic principles and alignment strategies, and applications in flexible electronics. Finally, future prospects are suggested to advance flexible electronics based on orderly arranged EHD direct‐written fibers. This technology overcomes the limitations of the resolution of fabrication and viscosity of ink of conventional inkjet printing, and represents major advances in manufacturing of flexible electronics.     

A Thin Carbon‐Fiber Web as a Scaffold for Bone‐Tissue Regeneration

Due to the rapid progress being made in tissue regeneration therapy, biomaterials used as scaffolds are expected to play an important role in future clinical application. We report the development of a 3D web (sheet) consisting of high‐purity carbon fibers in a nanoscale structure. When the thin carbon‐fiber web (TCFW) and recombinant human bone morphogenetic protein 2 (rhBMP‐2) composite is implanted in the murine back muscle, new ectopic bone is formed, and the values of the bone mineral content and bone mineral density are significantly higher than those obtained with a collagen sheet. Observation of the interface between the carbon fibers and bone matrix reveal that the fibers are directly integrated into the bone matrix, indicating high bone‐tissue compatibility. Further, the rhBMP‐2/TCFW composite repairs a critical‐size bone defect within a short time period. These results suggest that the TCFW functions as an effective scaffold material and will play an important role in tissue regeneration in the future.     

Dual Functional Modification of Alkaline Amino Acids Induces the Self‐Assembly of Cylinder‐Like Tobacco Mosaic Virus Coat Proteins into Gear‐Like Architectures

Herein, the assembly of 3D uniform gear‐like architectures is demonstrated with a tobacco mosaic virus (TMV) disk as a building block. In this context, the intrinsic behavior of the TMV disk that promotes its assembly into nanotubes is altered by a synergistic effect of dual functional modifications at the 53rd arginine mutation and the introduction of lysine groups in the periphery at 1st and 158th positions of the TMV disk, which results in the formation of 3D gear‐like superstructures. Therein, the 53rd arginine moiety significantly strengthens the linkage between TMV disks in the alkaline environment through hydrogen bond interactions. The charge of lysine‐modified lateral surfaces is partially neutralized in the alkaline solution, which induces the TMV disk to form a gear‐like architecture to maintain its structural stability by exploiting the electrostatic repulsion between neighboring TMV disks. This study not only provides explicit evidence regarding the molecular‐level understanding of how the modification of site‐specific amino acid affects the assembly of resultant superstructures but also encourages the fabrication of functional protein‐based nanoarchitectures.     

Photosensitizer‐Incorporated Quadruplex DNA‐Gated Nanovechicles for Light‐Triggered,Targeted Dual Drug Delivery to Cancer Cells

A novel light‐operated vehicle for targeted intracellular drug delivery is constructed using photosensitizer‐incorporated G‐quadruplex DNA‐capped mesoporous silica nanoparticles. Upon light irradiation, the photosensitizer generates ROS, causing the DNA capping to be cleaved and allowing cargo to be released. Importantly, this platform makes it possible to develop a drug‐carrier system for the synergistic combination of chemotherapy and PDT for cancer treatment with spatial/temporal control. Furthermore, the introducing of targeting ligands further improves tumor targeting efficiency. The excellent biocompatibility, cell‐specific intracellular drug delivery, and cellular uptake properties set up the basis for future biomedical application that require in vivo controlled, targeted drug delivery.     

Precise Two‐Photon Photodynamic Therapy using an Efficient Photosensitizer with Aggregation‐Induced Emission Characteristics

Two‐photon photodynamic therapy (PDT) is able to offer precise 3D manipulation of treatment volumes, providing a target level that is unattainable with current therapeutic techniques. The advancement of this technique is greatly hampered by the availability of photosensitizers with large two‐photon absorption (TPA) cross section, high reactive‐oxygen‐species (ROS) generation efficiency, and bright two‐photon fluorescence. Here, an effective photosensitizer with aggregation‐induced emission (AIE) characteristics is synthesized, characterized, and encapsulated into an amphiphilic block copolymer to form organic dots for two‐photon PDT applications. The AIE dots possess large TPA cross section, high ROS generation efficiency, and excellent photostability and biocompatibility, which overcomes the limitations of many conventional two‐photon photosensitizers. Outstanding therapeutic performance of the AIE dots in two‐photon PDT is demonstrated using in vitro cancer cell ablation and in vivo brain‐blood‐vessel closure as examples. This shows therapy precision up to 5 µm under two‐photon excitation.     

Minimizing the Heat Effect of Photodynamic Therapy Based on Inorganic Nanocomposites Mediated by 808 nm Near‐Infrared Light

Photodynamic therapy (PDT) based on photosensitizers (PSs) constructed with nanomaterials has become popular in cancer treatment, especially oral carcinoma cell. This therapy is characterized by improved PS accumulation in tumor regions and generation of reactive oxygen species (ROS) for PDT under specific excitation. In the selection of near‐infrared (NIR) window, 808 nm NIR light because it can avoid the absorption of water is particularly suitable for the application in PDT. Hence, multiband emissions under a single 808 nm near‐infrared excitation of Nd³⁺‐sensitized upconversion nanoparticles (808 nm UCNPs) have been applied for the PDT effect. 808 nm UCNPs serve as light converter to emit UV light to excite inorganic PS, graphitic carbon nitride quantum dots (CNQDs), thereby generating ROS. In this study, a nanocomposite consisting UCNPs conjugated with poly‐l ‐lysine (PLL) to improve binding with CNQDs is fabricated. According to the research results, NIR‐triggered nanocomposites of 808 nm UCNP‐PLL@CNs have been verified by significant improvement in ROS generation. Consequently, 808 nm UCNP‐PLL@CNs exhibit high capability for ROS production and efficient PDT in vitro and in vivo. Moreover, the mechanism of PDT treatment by 808 nm UCNP‐PLL@CNs is evaluated using the cell apoptosis pathway.     

OpenCL‐based implementation of an unstructured edge‐based finite element convection‐diffusion solver on graphics hardware

The solution of problems in computational fluid dynamics (CFD) represents a classical field for the application of advanced numerical methods. Many different approaches were developed over the years to address CFD applications. Good examples are finite volumes, finite differences (FD), and finite elements (FE) but also newer approaches such as the lattice‐Boltzmann (LB), smooth particle hydrodynamics or the particle finite element method. FD and LB methods on regular grids are known to be superior in terms of raw computing speed, but using such regular discretization represents an important limitation in dealing with complex geometries. Here, we concentrate on unstructured approaches which are less common in the GPU world. We employ a nonstandard FE approach which leverages an optimized edge‐based data structure allowing a highly parallel implementation. Such technique is applied to the ‘convection‐diffusion’ problem, which is often considered as a first step towards CFD because of similarities to the nonconservative form of the Navier–Stokes equations. In this regard, an existing highly optimized parallel OpenMP solver is ported to graphics hardware based on the OpenCL platform. The optimizations performed are discussed in detail. A number of benchmarks prove that the GPU‐accelerated OpenCL code consistently outperforms the OpenMP version. Copyright © 2011 John Wiley & Sons, Ltd.     

A Mussel‐Inspired Persistent ROS‐Scavenging,Electroactive, and Osteoinductive Scaffold Based on Electrochemical‐Driven In Situ Nanoassembly

Conductive polymers are promising for bone regeneration because they can regulate cell behavior through electrical stimulation; moreover, they are antioxidative agents that can be used to protect cells and tissues from damage originating from reactive oxygen species (ROS). However, conductive polymers lack affinity to cells and osteoinductivity, which limits their application in tissue engineering. Herein, an electroactive, cell affinitive, persistent ROS‐scavenging, and osteoinductive porous Ti scaffold is prepared by the on‐surface in situ assembly of a polypyrrole‐polydopamine‐hydroxyapatite (PPy‐PDA‐HA) film through a layer‐by‐layer pulse electrodeposition (LBL‐PED) method. During LBL‐PED, the PPy‐PDA nanoparticles (NPs) and HA NPs are in situ synthesized and uniformly coated on a porous scaffold from inside to outside. PDA is entangled with and doped into PPy to enhance the ROS scavenging rate of the scaffold and realize repeatable, efficient ROS scavenging over a long period of time. HA and electrical stimulation synergistically promote osteogenic cell differentiation on PPy‐PDA‐HA films. Ultimately, the PPy‐PDA‐HA porous scaffold provides excellent bone regeneration through the synergistic effects of electroactivity, cell affinity, and antioxidative activity of the PPy‐PDA NPs and the osteoinductivity of HA NPs. This study provides a new strategy for functionalizing porous scaffolds that show great promise as implants for tissue regeneration.     

Oxidation‐Responsive Nanoassemblies for Light‐Enhanced Gene Therapy

Microenvironment‐responsive supramolecular assemblies have attracted great interest in the biomedical field due to their potential applications in controlled drug release. In this study, oxidation‐responsive supramolecular polycationic assemblies named CPAs are prepared for nucleic acid delivery via the host–guest interaction of β‐cyclodextrin based polycations and a ferrocene‐functionalized zinc tetraaminophthalocyanine core. The reactive oxygen species (ROS) can accelerate the disassembly of CPA/pDNA complexes, which would facilitate the release of pDNA in the complexes and further benefit the subsequent transfection. Such improvement in transfection efficiency is proved in A549 cells with high H₂O₂ concentration. Interestingly, the transfection efficiencies mediated by CPAs are also different in the presence or absence of light in various cell lines such as HEK 293 and 4T1. The single oxygen (¹O₂), produced by photosensitizers in the core of CPAs under light, increases the ROS amount and accelerates the disassembly of CPAs/pDNA complexes. In vitro and in vivo studies further illustrate that suppressor tumor gene p53 delivered by CPAs exhibits great antitumor effects under illumination. This work provides a promising strategy for the design and fabrication of oxidation‐responsive nanoassemblies with light‐enhanced gene transfection performance.     

Electrochemical Monitoring of Paclitaxel‐Induced ROS Release from Mitochondria inside Single Cells

Mitochondria are believed to be the major source of intracellular reactive oxygen species (ROS). However, in situ, real‐time and quantitative monitoring of ROS release from mitochondria that are present in their cytosolic environment remains a great challenge. In this work, a platinized SiC@C nanowire electrode is placed into a single cell for in situ detection of ROS signals from intracellular mitochondria, and antineoplastic agent (paclitaxel) induced ROS production is successfully recorded. Further investigations indicate that complex IV (cytochrome c oxidase, COX) is the principal site for ROS generation, and significantly more ROS are generated from mitochondria in cancer cells than that from normal cells. This work provides an effective approach to directly monitor intracellular mitochondria by nanowire electrodes, and consequently obtains important physiological evidence on antineoplastic agent‐induced ROS generation, which will be of great benefit for better understanding of chemotherapy at subcellular levels.     

Metal–Organic‐Framework‐Derived Carbon Nanostructure Augmented Sonodynamic Cancer Therapy

Sonodynamic therapy (SDT) can overcome the critical issue of depth‐penetration barrier of photo‐triggered therapeutic modalities. However, the discovery of sonosensitizers with high sonosensitization efficacy and good stability is still a significant challenge. In this study, the great potential of a metal–organic‐framework (MOF)‐derived carbon nanostructure that contains porphyrin‐like metal centers (PMCS) to act as an excellent sonosensitizer is identified. Excitingly, the superior sonosensitization effect of PMCS is believed to be closely linked to the porphyrin‐like macrocycle in MOF‐derived nanostructure in comparison to amorphous carbon nanospheres, due to their large highest occupied molecular orbital (HOMO)–lowest unoccupied molecular orbital (LUMO) gap for high reactive oxygen species (ROS) production. The nanoparticle‐assisted cavitation process, including the visualized formation of the cavitation bubbles and microjets, is also first captured by high‐speed camera. High ROS production in PMCS under ultrasound is validated by electron spin resonance and dye measurement, followed by cellular destruction and high tumor inhibition efficiency (85%). This knowledge is important from the perspective of understanding the structure‐dependent SDT enhancement of a MOF‐derived carbon nanostructure.     

Stimulus‐Responsive Anti‐Oxidizing Drug Crystals and their Ecological Implication

Various antioxidants are being used to neutralize the harmful effects of reactive oxygen species (ROS) overproduced in diseased tissues and contaminated environments. Polymer‐directed crystallization of antioxidants has attracted attention as a way to control drug efficacy through molecular dissolution. However, most recrystallized antioxidants undertake continuous dissolution independent of the ROS level, thus causing side‐effects. This study demonstrates a unique method to assemble antioxidant crystals that modulate their dissolution rate in response to the ROS level. We hypothesized that antioxidants recrystallized using a ROS‐labile polymer would be triggered to dissolve when the ROS level increases. We examined this hypothesis by using catechin as a model antioxidant. Catechin was recrystallized using polyethylenimine cross‐linked with ROS‐labile diselanediylbis‐(ethane‐2,1‐diyl)‐diacrylate. Catechin crystallized with the ROS‐labile polymer displays accelerated dissolution proportional to the H₂O₂ concentration. The ROS‐responsive catechin crystals protect vascular cells from oxidative insults by activating intracellular glutathione peroxidase expression and, in turn, inhibiting an increase in the intracellular oxidative stress. In addition, ROS‐responsive catechin crystals alleviate changes in the heart rate of Daphnia magna in oxidative media. We propose that the results of this study would be broadly useful for improving the therapeutic efficacy of a broad array of drug compounds.     

Controlling Long‐Distance Photoactuation with Protein Additives

Long‐distance wireless actuation indicates precise remote control over materials, sensors, and devices that are widely utilized in biomedical, defence, disaster relief, deep ocean, and outer space applications to replace human work. Unlike radio frequency (RF) control, which has low tolerance toward electromagnetic interference (EMI), light control represents a promising method to overcome EMI. Nonetheless, long‐distance light‐controlled wireless actuation able to compete with RF control has not been achieved until now due to the lack of highly light‐sensitive actuator designs. Here, it is demonstrate that amyloid‐like protein aggregates can organize photomodule single‐layer reduced graphene oxide (rGO) into a well‐defined multilayer stack to display long‐distance photoactuation. The amyloid‐like proteinaceous component docks the rGO layers together to form a hybrid film, which can reliably adhere onto various material surfaces with robust interfacial adhesion. The sensitive photothermal effect and a fast bending in 1 s to switch a circuit are achieved after forming the film on a plastic substrate and irradiating the bilayer film with a blue laser from 100 m away. A photoactuation distance of 50 km can be further extrapolated based on a commercial high‐power laser. This study reveals the great potential of amyloid‐like aggregates in remote light control of robots and devices.     

Porous Electrospun Fibers with Self‐Sealing Functionality: An Enabling Strategy for Trapping Biomacromolecules

Stimuli‐responsive porous polymer materials have promising biomedical application due to their ability to trap and release biomacromolecules. In this work, a class of highly porous electrospun fibers is designed using polylactide as the polymer matrix and poly(ethylene oxide) as a porogen. Carbon nanotubes (CNTs) with different concentrations are further impregnated onto the fibers to achieve self‐sealing functionality induced by photothermal conversion upon light irradiation. The fibers with 0.4 mg mL^?1 of CNTs exhibit the optimum encapsulation efficiency of model biomacromolecules such as dextran, bovine serum albumin, and nucleic acids, although their photothermal conversion ability is slightly lower than the fibers with 0.8 mg mL^?1 of CNTs. Interestingly, reversible reopening of the surface pores is accomplished with the degradation of PLA, affording a further possibility for sustained release of biomacromolecules after encapsulation. Effects of CNT loading on fiber morphology, structure, thermal/mechanical properties, degradation, and cell viability are also investigated. This novel class of porous electrospun fibers with self‐sealing capability has great potential to serve as an enabling strategy for trapping/release of biomacromolecules with promising applications in, for example, preventing inflammatory diseases by scavenging cytokines from interstitial body fluids.     

Near‐Infrared Upconversion Mesoporous Cerium Oxide Hollow Biophotocatalyst for Concurrent pH‐/H2O2‐Responsive O2‐Evolving Synergetic Cancer Therapy

Tumor hypoxia is typically presented in the central region of solid tumors, which is mainly caused by an inadequate blood flow and oxygen supply. In the conventional treatment of hypoxic human tumors, not only the oxygen‐dependent photodynamic therapy (PDT), but also antitumor drug‐based chemotherapy, is considerably limited. The use of direct oxygen delivering approach with oxygen‐dependent PDT or chemotherapy may potentiate the reactive oxygen species (ROS)‐mediated cytotoxicity of the drug toward normal tissues. Herein, a synergetic one‐for‐all mesoporous cerium oxide upconversion biophotocatalyst is developed to achieve intratumorally endogenous H₂O₂‐responsive self‐sufficiency of O₂ and near‐infrared light controlled PDT simultaneously for overcoming hypoxia cancer. Furthermore, the sufficient O₂ plays an important role in overcoming the chemotherapeutic drug‐resistant cancer caused by hypoxia, therefore inducing tumor cell apoptosis significantly.     

Junction‐Free Electrospun Ag Fiber Electrodes for Flexible Organic Light‐Emitting Diodes

Fabrication of junction‐free Ag fiber electrodes for flexible organic light‐emitting diodes (OLEDs) is demonstrated. The junction‐free Ag fiber electrodes are fabricated by electrospun polymer fibers used as an etch mask and wet etching of Ag thin film. This process facilitates surface roughness control, which is important in transparent electrodes based on metal wires to prevent electrical instability of the OLEDs. The transmittance and resistance of Ag fiber electrodes can be independently adjusted by controlling spinning time and Ag deposition thickness. The Ag fiber electrode shows a transmittance of 91.8% (at 550 nm) at a sheet resistance of 22.3 Ω □^?1, leading to the highest OLED efficiency. In addition, Ag fiber electrodes exhibit excellent mechanical durability, as shown by measuring the change in resistance under repeatable mechanical bending and various bending radii. The OLEDs with Ag fiber electrodes on a flexible substrate are successfully fabricated, and the OLEDs show an enhancement of EQE (≈19%) compared to commercial indium tin oxide electrodes.     

Out‐of‐Plane 3D‐Printed Microfibers Improve the Shear Properties of Hydrogel Composites

One challenge in biofabrication is to fabricate a matrix that is soft enough to elicit optimal cell behavior while possessing the strength required to withstand the mechanical load that the matrix is subjected to once implanted in the body. Here, melt electrowriting (MEW) is used to direct‐write poly(ε‐caprolactone) fibers “out‐of‐plane” by design. These out‐of‐plane fibers are specifically intended to stabilize an existing structure and subsequently improve the shear modulus of hydrogel–fiber composites. The stabilizing fibers (diameter = 13.3 ± 0.3 µm) are sinusoidally direct‐written over an existing MEW wall‐like structure (330 µm height). The printed constructs are embedded in different hydrogels (5, 10, and 15 wt% polyacrylamide; 65% poly(2‐hydroxyethyl methacrylate) (pHEMA)) and a frequency sweep test (0.05–500 rad s^?1, 0.01% strain, n = 5) is performed to measure the complex shear modulus. For the rheological measurements, stabilizing fibers are deposited with a radial‐architecture prior to embedding to correspond to the direction of the stabilizing fibers with the loading of the rheometer. Stabilizing fibers increase the complex shear modulus irrespective of the percentage of gel or crosslinking density. The capacity of MEW to produce well‐defined out‐of‐plane fibers and the ability to increase the shear properties of fiber‐reinforced hydrogel composites are highlighted.