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The development of semiconducting polymers (SPs) with simultaneous second near‐infrared (NIR‐II) absorption and multimodal phototheranostic functions is highly desired in the field of oncotherapy. Aggregation‐induced emission luminogens (AIEgens) have been acknowledged to possess unique potential in integrating multiple diagnostic and therapeutic modalities into one organic molecule. Nevertheless, SPs are hard to achieve AIE activity due to their extended π‐conjugated skeletons as well as the large and planar configuration of commonly‐used electrophilic acceptor moieties. Herein, an ingenious acceptor dimerization‐based acceptor distortion strategy is proposed in current work by taking advantage of the sterically encumbered acceptors with large and planar structure for the successful construction of AIE‐active SPs. Through further finely adjusting the molecular donor–acceptor interaction strength, one of the obtained AIE‐active SPs named SP3 bearing the highest intramolecular charge transfer effect presented desired NIR‐II absorption and aggregation‐induced NIR‐II fluorescence emission, good reactive oxygen species production ability, as well as superior photothermal conversion performance. Accordingly, SP3 is selected to fabricate into nanoparticles and successfully applied in the NIR‐II laser‐triggered fluorescence‐photoacoustic imaging‐guided photodynamic‐photothermal therapy of tumors. This study represents the first NIR‐II excitable AIE‐active SP, and offers a new perspective on designing advanced multimodal phototheranostic polymers for efficient treatment of malignant tumor. [ABSTRACT FROM AUTHOR]

Despite recent advances in colloidal hydrogels, designing general and robust strategies that enable the controlled fabrication of colloidal hydrogels with strong mechanical properties still proves challenging. Herein, the statistical copolymerization‐induced self‐assembly (stat‐PISA) of monomers with hydrogen bonding ability is developed as a general strategy for colloidal hydrogels with high stretchability, anti‐swelling, and self‐healing abilities. This concept is first verified by the statistical dispersion copolymerization of acrylic acid and diacetone acrylamide, yielding statistical copolymer colloidal particles that further coalesced into a 3D colloidal network due to the hydrogen bonding interactions and hydrophobic microdomains on the colloidal surface. Both the microstructure and the mechanical properties of the colloidal hydrogels can be readily regulated by varying the stat‐PISA formulation. Besides, the colloidal hydrogel is developed as a selective dye adsorbent, with excellent selectivity for positively charged dyes. Due to its anti‐swelling property, the colloidal hydrogel is evaluated as a flexible strain sensor for motion detection underwater. The broad feasibility of this strategy is demonstrated by three additional stat‐PISA formulations, which all yielded colloidal hydrogels with good mechanical properties. This strategy is anticipated to inspire the design of colloidal hydrogels with robust mechanics and tailor‐made functionality, and broaden the potential applications of colloidal hydrogels. [ABSTRACT FROM AUTHOR]

Janus 2D materials have drawn substantial attention recently owing to its extraordinary interface properties and promising applications in optoelectronic devices. However, the scalable fabrication of high‐quality Janus 2D materials is still one of the main obstacles to hinder its implementation in the industry. Herein, a new method (called "chemical breakdown") is developed to obtain large‐area uniform Janus graphene oxide (J‐GO) films with high‐quality. Moreover, the first application of J‐GO in the field of memristive devices is presented for neuromorphic computing. In particular, crossbar arrays of Ag/J‐GO/Au memristive devices that exhibit threshold resistive switching (RS) with enhanced performance are fabricated, e.g., low leakage current (≈10−12 A), low operation voltage (≈0.3 V), high endurance (>12,000 cycles), and electro‐synaptic plasticity. This work provides a novel strategy to obtain large‐area, continuous and uniform Janus 2D films, and proposes a new application for Janus 2D materials in a hot topic (i.e., neuromorphic computing) within the field of solid‐state microelectronics. [ABSTRACT FROM AUTHOR]

Three‐photon fluorescence (3PF) imaging excited at 1700 nm window is an enabling technology for visualizing deep brain structures and dynamics. Recently, the 2200 nm window has emerged as the longest excitation window suitable for deep‐brain 3PF imaging. Bright fluorescent probes lay the material basis for deep‐brain 3PF imaging. Among various fluorescent probes, aggregation‐induced emission luminogens (AIEgens) have great potential in 3PF imaging excited at the 1700 nm window in vivo. However, to the best of knowledge, there is no AIEgens applicable to 3PF imaging excited at both the 1700 and 2200 nm windows. To readily fill this gap, here this study designs and synthesizes a novel AIEgen, namely TPE‐DPTT‐ICP, which generates bright 3PF signals excited at both 1700 and 2200 nm. The accordingly fabricated TPE‐DPTT‐ICP nanoparticles (NPs) possess excellent water dispersibility, colloidal stability, biocompatibility, photostability and large 3P action cross section, key to in vivo imaging. In mouse brain in vivo, TPE‐DPTT‐ICP NPs enable deep‐brain 3PF imaging of subcortical structures excited at both the two windows, reaching depths of 1640 and 880 µm below the brain surface, respectively. TPE‐DPTT‐ICP NPs are thus a versatile material simultaneously catering to the need at two infrared optical windows with deep tissue penetration. [ABSTRACT FROM AUTHOR]

The progression of osteoarthritis is associated with chronic synovitis caused by synovial macrophage infiltration and proinflammatory M1 polarization. Accordingly, repolarization of macrophages from the M1 to M2 phenotype by nanoagents is proposed as a potential treatment strategy. However, achieving adequate effects using intra‐articular injected agents is challenging due to the rapid drug clearance from the joint space and poor efficiency of nanoparticles endocytosis by synovial macrophage cells. Herein, apoptotic chondrocyte membrane‐coated, quercetin‐loaded metal‐organic framework nanoparticles as immunomodulators for treating osteoarthritis are reported. The apoptotic chondrocyte membrane‐camouflaged nanoparticles containing various natural "eat me" signals can be easily disguised as chondrocyte apoptotic bodies in the joints, and thus are more easily phagocytized by synovial macrophages similarly to efferocytosis. Furthermore, the released quercetin promotes the polarization of synovial macrophages to the M2 phenotype and also inhibites the apoptosis of articular chondrocytes. In vivo results suggest that such a "Trojan horse" strategy can extend the retention time of nanoparticles in osteoarthritis joints and improve treatment efficacy. Collectively, it is hoped that this study can offer a potential and universal platform for engineered cell membrane‐coated nanoparticles to resolve inflammation by simulating specific inflammatory processes. [ABSTRACT FROM AUTHOR]

Fluorophores lay the material basis for tissue labeling and fluorescence imaging, especially for deep‐brain multiphoton microscopy (MPM) in animal models. Among various fluorescent materials, those with aggregation‐induced emission (AIE) characteristics, i.e., AIEgens, have excellent optical properties and biocompatibility and thus have found widespread applications in biomedical imaging. However, their application to deep‐brain MPM has so far been limited in imaging depth, which undoubtedly poses a hindrance to neurological research aiming to probe the deeper brain. In order to address the issue, here a novel bright AIEgen, namely MTTCM, is designed and synthesized via facile reactions routes. The self‐assembled MTTCM nanoparticles (NPs) with their water‐dispersible feature, have good biocompatibility and good photostability. Furthermore, they are spectrally advantageous for deep‐brain MPM: their emission lies in the NIR‐I region, they generate 3‐photon fluorescence with NIR‐III excitation and show only a slight blue‐shift in the emitted 3‐photon fluorescence in vivo. From a fundamental photochemical perspective, it is also confrimed that MTTCM NPs obey Kasha's rule since the measured 3‐photon and 1‐photon fluorescence spectra overlap. All these merits make MTTCM NPs the enabling fluorophores for record depth in brain imaging in vivo: 1905 µm after craniotomy and 1100 µm through an intact skull, excited at 1660 nm. Furthermore, a record 752 µm hemodynamic imaging depth before craniotomy is demonstrated, from which the blood flow speed can be measured. MTTCM NPs are thus promising fluorophores for deep‐brain 3‐photon imaging in vivo. [ABSTRACT FROM AUTHOR]

Construction of versatile nanotemplate bearing inherent distinctive functions and prominent drug‐carrying capability is an appealing yet significantly challenging task. Here, inspired by the guiding role of surfactant in preparing nanoparticles, an amphiphilic aggregation‐induced emission (AIE) photosensitizer, namely MeOTTVP, is synthesized with attractive near‐infrared (NIR) emission and high‐performance reactive oxygen species production, and followed by dual‐templating‐assisted one‐pot method involving MeOTTVP as the skeleton to fabricate organosilica nanoparticles (AIE‐ONs). The presented AIE‐ONs perfectly inherit the functions of MeOTTVP, and are also capable of loading antibiotics and anticancer drugs. Doxorubicin can be assembled on AIE‐ONs and then capped with hyaluronic acid, endowing the resulting hybrid with NIR fluorescence imaging‐guided synergetic photodynamic/chemotherapy performance, thereby offering boosted anticancer efficacy and reduced side effects. Furthermore, by loading antibiotic rifampicin, the newly obtained AIE‐ONs integrating chemo‐photodynamic antibacterial functions provide broad‐spectrum antibacterial activity and fluorescence monitoring behavior. This study thus not only offers a promising strategy to fabricate NIR nanoparticles on a large scale, but also provides useful insights into designing an advanced theranostic protocol for treating both cancer and bacterial infections. [ABSTRACT FROM AUTHOR]

The ingenious construction of versatile cancer phototheranostics involving fluorescence imaging (FLI) and photodynamic and photothermal therapies (PDT, PTT) concurrently has attracted great interest. By virtue of their inherent twisted structures and plentiful motion moieties, aggregation‐induced emission luminogens (AIEgens) have been proven to be perfect templates for the development of multimodal phototheranostic systems as their diverse energy consumption pathways can be flexibly regulated through tuning the intramolecular motions. Side‐chain engineering is generally accepted as a useful regulation strategy for intramolecular motions through altering the side‐chain structure of the molecule, but has rarely been reported for the construction of AIE‐active multimodal phototheranostics. Herein, by taking full advantage of the side‐chain engineering strategy, an AIE‐active multifunctional phototheranostic system (TBFT2 nanoparticles) is successfully constructed by intentionally manipulating the length of side chains. Bearing the longest alkyl chain, all of those three energy dissipation pathways including radiative decay, nonradiative thermal deactivation, and intersystem crossing process of TBFT2 are retained simultaneously and controllably in the aggregate state. In vitro and in vivo evaluations verify that TBFT2 nanoparticles perform well in terms of FLI‐guided PDT and PTT synergistic cancer therapy. This study thus provides new insight into the exploration of superior versatile phototheranostics through side‐chain engineering. [ABSTRACT FROM AUTHOR]

Supramolecular approaches have opened up vast possibilities to construct versatile materials, especially those with stimuli‐responsiveness and integrated functionalities of multi‐modal diagnosis and synergistic therapeutics. In this study, a hybrid theranostic nanosystem named TTPY‐Py⊂CP5@AuNR is constructed via facile host–guest interactions, where TTPY‐Py is a photosensitizer with aggregation‐induced emission and CP5@AuNR represents the carboxylatopillar[5]arene (CP5)‐modified Au nanorods. TTPY‐Py⊂CP5@AuNR integrates the respective advantages of TTPY‐Py and CP5@AuNR such as the high performance of reactive oxygen species generation and photothermal conversion, and meanwhile shows fluorescence responses to both temperature and pH stimuli. The successful modification of CP5 macrocycles on AuNRs surfaces can eliminate the cytotoxicity of AuNRs and enable them to serve as the nanocarrier of TTPY‐Py for further theranostic applications. Significantly, in vitro and in vivo evaluations demonstrate that this supramolecular nanotheranostic system possesses multiple modalities including intensive fluorescence imaging (FLI), photoacoustic imaging (PAI), efficient photodynamic therapy (PDT), and photothermal therapy (PTT), indicating its great potential for FLI‐PAI imaging‐guided synergistic PDT‐PTT therapy. Moreover, TTPY‐Py can be released upon activation by the acidic environment of lysosomes and then specifically light up mitochondria. This study demonstrates a new strategy for the design of versatile nanotheranostics for accurate tumor imaging and cancer therapies. [ABSTRACT FROM AUTHOR]

Fluorescence imaging in the second near‐infrared region (NIR‐II) can penetrate tissue at centimeter depths and obtain high image fidelity. However, facile synthesis of small‐molecule fluorescent photosensitizers for efficient NIR‐II fluorescence imaging as well as photodynamic and photothermal combinatorial therapies is still a challenging task. Herein, a rational design and facile synthesis protocol are reported for a series of novel NIR‐emissive zwitterionic luminogens with aggregation‐induced emission (AIE) features for cancer phototheranostics. Consistent with the intrinsic features including long emission wavelength, effective reactive oxygen species generation, and excellent photothermal conversion efficiency (35.76%), in vitro and in vivo evaluation show that one of these presented AIE luminogens provides excellent performance in NIR‐II fluorescence imaging‐guided synergistic phototherapy against cancer. [ABSTRACT FROM AUTHOR]

Enzyme replacement therapy (ERT) holds great potential for treating enzyme deficiency related diseases. However, the enzymic vulnerability and the undesirable toxic side effects have strongly limited its clinical applications. Here a novel artificial metalloenzyme-based ERT with significant self-protection and toxic self-cleaning ability is developed for the treatment of hyperuricemia. The uricase and platinum nanoparticles (PtNPs) are closely confined in the pores of mesoporous silica nanoparticles and encapsulated within a silica defense layer to form a tandem catalytic system. This artificial metalloenzyme keeps a high uric acid (UA) degradation activity, as well as a strong resistance capability toward various insults, such as pH, high temperature, and protease. Besides, the H2O2 produced by UA can be simultaneously eliminated by the PtNPs, resulting in significant improvement on the mammalian cell viability. In vivo studies display prominent therapy effect and no obvious side effects during the treatment of hyperuricemia mice using this artificial metalloenzyme. These results provide new insights into development of efficient and friendly enzyme replacement therapy. [ABSTRACT FROM AUTHOR]

Herein, multifunctional mimics of viral architectures and infections self-assembled from tailor-made dendritic lipopeptides for programmed targeted drug delivery are reported. These viral mimics not only have virus-like components and nanostructures, but also possess virus-like infections to solid tumor and tumor cells. Encouragingly, the viral mimics provide the following distinguished features for tumor-specific systemic delivery: i) stealthy surface to resist protein interactions and prolong circulation time in blood, ii) well-defined nanostructure for passive targeting to solid tumor site, iii) charge-tunable shielding for tumor extracellular pH targeting, iv) receptor-mediated targeting to enhance tumor-specific uptake, and v) supramolecular lysine-rich architectures mimicking viral subcellular targeting for efficient endosomal escape and nuclear delivery. This bioinspired design make in vivo tumor suppression by drug-loaded viral mimics against BALB/c mice bearing 4T1 tumor greatly exceed the positive control group (more than three times). More importantly, viral mimics hold great potentials to reduce side effects and decrease tumor metastasis after systemic administration. [ABSTRACT FROM AUTHOR]

Quantitatively tracking engraftment of intracerebrally or intravenously transplanted stem cells and evaluating their concomitant therapeutic efficacy for stroke has been a challenge in the field of stem cell therapy. In this study, first, an MRI/SPECT/fluorescent tri-modal probe (125I-fSiO4@SPIOs) is synthesized for quantitatively tracking mesenchymal stem cells (MSCs) transplanted intracerebrally or intravenously into stroke rats, and then the therapeutic efficacy of MSCs delivered by both routes and the possible mechanism of the therapy are evaluated. It is demonstrated that (125)I-fSiO4@SPIOs have high efficiency for labeling MSCs without affecting their viability, differentiation, and proliferation capacity , and found that 35% of intracerebrally injected MSCs migrate along the corpus callosum to the lesion area, while 90% of intravenously injected MSCs remain trapped in the lung at 14 days after MSC transplantation. However, neurobehavioral outcomes are significantly improved in both transplantation groups, which are accompanied by increases of vascular endothelial growth factor, basic fibroblast growth factor, and tissue inhibitor of metalloproteinases-3 in blood, lung, and brain tissue ( p < 0.05). The study demonstrates that 125I-fSiO4@SPIOs are robust probe for long-term tracking of MSCs in the treatment of ischemic brain and MSCs delivered via both routes improve neurobehavioral outcomes in ischemic rats. [ABSTRACT FROM AUTHOR]

Stimuli-responsive anticancer agents are of particular interest in the field of cancer therapy. Nevertheless, so far stimuli-responsive photothermal agents have been explored with limited success for cancer photothermal therapy (PTT). In this work, as a proof-of-concept, a pH-responsive photothermal nanoconjugate for enhanced PTT efficacy, in which graphene oxide (GO) with broad NIR absorbance and effective photothermal conversion efficiency is selected as a typical model receptor of fluorescence resonance energy transfer (FRET), and grafted cyanine dye (e.g., Cypate) acts as the donor of near-infrared fluorescence (NIRF), is reported for the first time. The conjugate of Cypate-grafted GO exhibits different conformations in aqueous solutions at various pH, which can trigger pH-dependent FRET effect between GO and Cypate and thus induce pH-responsive photothermal effect of GO-Cypate. GO-Cypate exhibits severe cell damage owing to the enhanced photothermal effect in lysosomes, and thus generate synergistic PTT efficacy with tumor ablation upon photoirradiation after a single-dose intravenous injection. The photothermal nanoconjugate with broad NIR absorbance as the effective receptor of FRET can smartly convert emitted NIRF energy from donor cyanine dye into additional photothermal effect for improving PTT. These results suggest that the smart nanoconjugate can act as a promising stimuli-responsive photothermal nanoplatform for cancer therapy. [ABSTRACT FROM AUTHOR]

Adjuvants play an important role in vaccines. Alum and MF59 are two dominant kinds of adjuvants used in humans. Both of them, however, have limited capacity to generate the cellular immune response required for vaccines against cancers and viral diseases. It is desirable to develop new and efficient adjuvants with the aim of improving the cellular immune response against the antigen. Here, the feasibility and efficiency of ultrasmall graphene oxide supported gold nanoparticles (usGO-Au) as a new immune adjuvant to improve immune responses are explored. usGO-Au is obtained from reduction of chloroauric acid using usGO and then decorated with ovalbumin (OVA, a model antigen) through physical adsorption to construct usGO-Au@OVA. As the results show, the as-synthesized usGO-Au@OVA can efficiently stimulate RAW264.7 cells to secrete tumor necrosis factor-α (TNF-α), a mediator for cellular immune response. In vivo studies demonstrate that usGO-Au@OVA can also promote robust OVA specific antibody response, CD8+ T cells proliferation, and different cytokines secretion. The results indicate that using usGO-Au as an adjuvant can stimulate potent humoral and cellular immune responses against antigens, which may promote better understanding of cellular immune response and facilitate potential applications for cancer and viral vaccines. [ABSTRACT FROM AUTHOR]

X. Xu, Z. Gu, and co‐workers show on page 5250 that dendritic lipopeptide‐based mimics of viral architectures can serve as a versatile nanoplatform for tumor‐targeted drug delivery. The receptor‐mediated targeting and subcellular targeting can greatly promote therapeutic index of antitumor drugs, reducing side effects and decreasing tumor metastasis after systemic administration. [ABSTRACT FROM AUTHOR]

On page 1024 C. Zhang, G.‐Y. Yang, and co‐workers synthesize an MRI/SPECT/fluorescent tri‐modal probe to label mesenchymal stem cells, and evaluate the cell delivery routes on the distribution of cell in vivo and the concomitant therapeutic effects using a rat ischemic stroke model. They find that cell delivery routes significantly affect the cell distribution, but don't affect the therapeutic efficacy of the cells on ischemic brain. [ABSTRACT FROM AUTHOR]

On page 59, Z. J. Zhang, H. B. Chen, and co‐workers explore a pH‐responsive photothermal nanoconjugate, in which grafted cyanine dye acts as the donor of near‐infrared fluorescence (NIRF) and graphene oxide with broad NIR absorbance and effective photothermal conversion efficiency is selected as a typical receptor of fluorescence resonance energy transfer (FRET), for enhanced photothermal therapy with tumor ablation. [ABSTRACT FROM AUTHOR]