Biomimetic Self-Propelled Asymmetric Nanomotors for Cascade-Targeted Treatment of Neurological Inflammation.

The precise targeted delivery of therapeutic agents to deep regions of the brain is crucial for the effective treatment of various neurological diseases. However, achieving this goal is challenging due to the presence of the blood‒brain barrier (BBB) and the complex anatomy of the brain. Here, a biomimetic self-propelled nanomotor with cascade targeting capacity is developed for the treatment of neurological inflammatory diseases. The self-propelled nanomotors are designed with biomimetic asymmetric structures with a mesoporous SiO2 head and multiple MnO2 tentacles. Macrophage membrane biomimetic modification endows nanomotors with inflammatory targeting and BBB penetration abilities The MnO2 agents catalyze the degradation of H2O2 into O2, not only by reducing brain inflammation but also by providing the driving force for deep brain penetration. Additionally, the mesoporous SiO2 head is loaded with curcumin, which actively regulates macrophage polarization from the M1 to the M2 phenotype. All in vitro cell, organoid model, and in vivo animal experiments confirmed the effectiveness of the biomimetic self-propelled nanomotors in precise targeting, deep brain penetration, anti-inflammatory, and nervous system function maintenance. Therefore, this study introduces a platform of biomimetic self-propelled nanomotors with inflammation targeting ability and active deep penetration for the treatment of neurological inflammation diseases.

Drug-Free Antimicrobial Nanomotor for Precise Treatment of Multidrug-Resistant Bacterial Infections.

Manufacturing heteronanostructures with specific physicochemical characteristics and tightly controllable designs is very appealing. Herein, we reported NIR-II light-driven dual plasmonic (AuNR-SiO2-Cu7S4) antimicrobial nanomotors with an intended Janus configuration through the overgrowth of copper-rich Cu7S4 nanocrystals at only one high-curvature site of Au nanorods (Au NRs). These nanomotors were applied for photoacoustic imaging (PAI)-guided synergistic photothermal and photocatalytic treatment of bacterial infections. Both the photothermal performance and photocatalytic activity of the nanomotors are dramatically improved owing to the strong plasmon coupling between Au NRs and the Cu7S4 component and enhanced energy transfer. The motion behavior of nanomotors promotes transdermal penetration and enhances the matter-bacteria interaction. More importantly, the directional navigation and synergistic antimicrobial activity of the nanomotors could be synchronously driven by NIR-II light. The marriage of active motion and enhanced antibacterial activity resulted in the expected good antibacterial effects in an abscess infection mouse model.

Hypoxia-Responsive Aggregation of Gold Nanoparticles for Near-Infrared-II Photoacoustic Imaging-Guided Enhanced Radiotherapy.

By directly harming cancer cells, radiotherapy (RT) is a crucial therapeutic approach for the treatment of cancers. However, the efficacy of RT is reduced by the limited accumulation and short retention time of the radiosensitizer in the tumor. Herein, we developed hypoxia-triggered in situ aggregation of nanogapped gold nanospheres (AuNNP@PAA/NIC NPs) within the tumor, resulting in second near-infrared window (NIR-II) photoacoustic (PA) imaging and enhanced radiosensitization. AuNNP@PAA/NIC NPs demonstrated increased accumulation and retention in hypoxic tumors, mainly due to the hypoxia-triggered aggregation. After aggregation of AuNNP@PAA/NIC NPs, the absorption of the system extended from visible light to NIR-II light owing to the plasmon coupling effects between adjacent nanoparticles. Compared to the normoxic tumor, the PA intensity at 1200 nm in the hypoxic tumor increased from 0.42 to 1.88 at 24 h postintravenous injection of AuNNP@PAA/NIC NPs, leading to an increase of 4.5 times. This indicated that the hypoxic microenvironment in the tumor successfully triggered the in situ aggregation of AuNNP@PAA/NIC NPs. The in vivo radiotherapeutic effect demonstrated that this hypoxia-triggered in situ aggregation of radiosensitizers significantly enhanced radiosensitization and thus resulted in superior cancer radiotherapeutic outcomes.

Design and synthesis of a small molecular NIR-II chemiluminescence probe for in vivo-activated H2S imaging.

Chemiluminescence (CL) with the elimination of excitation light and minimal autofluorescence interference has been wieldy applied in biosensing and bioimaging. However, the traditional emission of CL probes was mainly in the range of 400 to 650 nm, leading to undesired resolution and penetration in a biological object. Therefore, it was urgent to develop CL molecules in the near-infrared window [NIR, including NIR-I (650 to 900 nm) and near-infrared-II (900 to 1,700 nm)], coupled with unique advantages of long-time imaging, sensitive response, and high resolution at depths of millimeters. However, no NIR-II CL unimolecular probe has been reported until now. Herein, we developed an H2S-activated NIR-II CL probe [chemiluminiscence donor 950, (CD-950)] by covalently connecting two Schaap's dioxetane donors with high chemical energy to a NIR-II fluorophore acceptor candidate via intramolecular CL resonance energy transfer strategy, thereby achieving high efficiency of 95%. CD-950 exhibited superior capacity including long-duration imaging (~60 min), deeper tissue penetration (~10 mm), and specific H2S response under physiological conditions. More importantly, CD-950 showed detection capability for metformin-induced hepatotoxicity with 2.5-fold higher signal-to-background ratios than that of NIR-II fluorescence mode. The unimolecular NIR-II CL probe holds great potential for the evaluation of drug-induced side effects by tracking its metabolites in vivo, further facilitating the rational design of novel NIR-II CL-based detection platforms.

Plasmon enhanced catalysis-driven nanomotors with autonomous navigation for deep cancer imaging and enhanced radiotherapy.

Radiosensitizers potentiate the radiotherapy effect while effectively reducing the damage to healthy tissues. However, limited sample accumulation efficiency and low radiation energy deposition in the tumor significantly reduce the therapeutic effect. Herein, we developed multifunctional photocatalysis-powered dandelion-like nanomotors composed of amorphous TiO2 components and Au nanorods (∼93 nm in length and ∼16 nm in outer diameter) by a ligand-mediated interface regulation strategy for NIR-II photoacoustic imaging-guided synergistically enhanced cancer radiotherapy. The non-centrosymmetric nanostructure generates stronger local plasmonic near-fields close to the Au-TiO2 interface. Moreover, the Au-TiO2 Schottky heterojunction greatly facilitates the separation of photogenerated electron-hole pairs, enabling hot electron injection, finally leading to highly efficient plasmon-enhanced photocatalytic activity. The nanomotors exhibit superior motility both in vitro and in vivo, propelled by H2 generated via NIR-catalysis on one side of the Au nanorod, which prevents them from returning to circulation and effectively improves the sample accumulation in the tumor. Additionally, a high radiation dose deposition in the form of more hydroxyl radical generation and glutathione depletion is authenticated. Thus, synergistically enhanced radiotherapeutic efficacy is achieved in both a subcutaneous tumor model and an orthotopic model.

Spatiotemporally Controlled Formation and Rotation of Magnetic Nanochains In Vivo for Precise Mechanotherapy of Tumors.

Systemic cancer therapy is always accompanied with toxicity to normal tissue, which has prompted concerted efforts to develop precise treatment strategies. Herein, we firstly develop an approach that enables spatiotemporally controlled formation and rotation of magnetic nanochains in vivo, allowing for precise mechanotherapy of tumor. The nanochain comprised nanocomposites of pheophorbide-A (PP) modified iron oxide nanoparticle (IONP) and lanthanide-doped down-conversion NP (DCNP). In a permanent magnetic field, the nanocomposites would be aligned to form nanochain. Next, MnO2 NPs were subsequently administered to accumulate in tumor as suppliers of Mn2+ , which coordinates with PP to immobilize the nanochain. In a rotating magnetic field, the nanochain would rapidly rotate, leading to apoptosis/necrosis of tumor cell. The nanochain showed high T2 -MR and NIR-II fluorescence imaging signals, which facilitated guided therapy. The strategy has great potential in practical applications.

In-Situ Assembly of Janus Nanoprobe for Cancer Activated NIR-II Photoacoustic Imaging and Enhanced Photodynamic Therapy.

Inorganic nanoprobes have attracted increasing attention in the biomedical field due to their versatile functionalities and excellent optical properties. However, conventional nanoprobes have a relatively low retention time in the tumor and are mostly applied in the first near-infrared window (NIR-I, 650-950 nm), limiting their applications in accurate and deep tissue imaging. Herein, we develop a Janus nanoprobe, which can undergo tumor microenvironment (TME)-induced aggregation, hence, promoting tumor retention time and providing photoacoustic (PA) imaging in the second NIR (NIR-II, 950-1700 nm) window, and enhancing photodynamic therapy (PDT) effect. Ternary Janus nanoprobe is composed of gold nanorod (AuNR) coated with manganese dioxide (MnO2) and photosensitizer pyropheophorbide-a (Ppa) on two ends of AuNR, respectively, named as MnO2-AuNR-Ppa. In the tumor, MnO2 could be etched by glutathione (GSH) to release Mn2+, which is coordinated with multiple Ppa molecules to induce in situ aggregation of AuNRs. The aggregation of AuNR effectively improves the NIR-II photoacoustic signal in vivo. Moreover, the increased retention time of nanoprobes and GSH reduction in the tumor greatly improve the PDT effect. We believe that this work will inspire further research on specific in situ aggregation of inorganic nanoparticles.

Nanosized Janus AuNR-Pt Motor for Enhancing NIR-II Photoacoustic Imaging of Deep Tumor and Pt2+ Ion-Based Chemotherapy.

Synthetic micro/nanomotors have great potential in deep tissue imaging and in vivo drug delivery because of their active motion ability. However, applying nanomotors with a size less than 100 nm to in vivo imaging and therapy is one of the core changes in this field. Herein, a nanosized hydrogen peroxide (H2O2)-driven Janus gold nanorod-platinum (JAuNR-Pt) nanomotor is developed for enhancing the second near-infrared region (NIR-II) photoacoustic (PA) imaging of deep tissues of tumors and for effective tumor treatment. The JAuNR-Pt nanomotor is prepared by depositing platinum (Pt) on one end of a gold nanorod with varying proportions of Pt shell coverage, including 10%, 25%, 50%, 75%, and 100%. The JAuNR-Pt nanomotor with Pt shell coverage proportions of 50% exhibits the highest diffusion coefficient (De), and it can rapidly move in the presence of H2O2. The self-propulsion of JAuNR-Pt nanomotor enhances cellular uptake, accelerates lysosomal escape, and facilitates continuous release of cytotoxic Pt2+ ions to the nucleus, causing DNA damage and cell apoptosis. The JAuNR-Pt nanomotor presents deep penetration and enhanced accumulation in tumors as well as high tumor treatment effect. Therefore, this work displays deep tumor imaging and an excellent antitumor effect, providing an effective tool for accurate diagnosis and treatment of diseases.

An Activatable Hybrid Organic-Inorganic Nanocomposite as Early Evaluation System of Therapy Effect.

Delays in evaluating cancer response to radiotherapy (RT) usually reduce therapy effect or miss the right time for treatment optimization. Hence, exploring timely and accurate methods enabling one to gain insights of RT response are highly desirable. In this study, we have developed an apoptosis enzyme (caspase-3) activated nanoprobe for early evaluation of RT efficacy. The nanoprobe bridged the nanogapped gold nanoparticles (AuNNPs) and the second near-infrared window (NIR-II) fluorescent (FL) molecules (IR-1048) through a caspase-3 specific peptide sequence (DEVD) (AuNNP@DEVD-IR1048). After X-ray irradiation, caspase-3 was activated to cut DEVD, turning on both NIR-II FL and PA imaging signals. The increased NIR-II FL/PA signals exhibited a positive correlation with the content of caspase-3. Moreover, the amount of the activated caspase-3 was negatively correlated with the tumor size. The results underscore the role of the caspase-3 activated by X-ray irradiation in bridging the imaging signals variation and tumor inhibition rate. Overall, activatable NIR-II FL/PA imaging was successfully used to timely predict and evaluate the RT efficacy. The evaluation system based on biomarker-triggered living imaging has the capacity to guide treatment decisions for numerous cancer types.

Photoreductive BiOCl Ultrathin Nanosheets for Highly Efficient Photocatalytic Color Switching.

The reversible photocatalytic color switching systems (PCSSs) driven by semiconductor nanoparticles have attracted considerable attention because of their wide applications. However, the developed semiconductor nanoparticles with photoreductive activity are mainly limited to TiO2-based photocatalysts, which greatly hinder their broad applications. Here we report a cocapping ligand-assisted strategy for the development of photoreductive BiOCl ultrathin nanosheets with abundant oxygen vacancies. Both the cocapping ligands and oxygen vacancies in BiOCl ultrathin nanosheets act as sacrificial electron donors to efficiently scavenge the photogenerated holes, endowing the BiOCl ultrathin nanosheets high photoreductive activity and thus enabling the photocatalytic color switching of redox dyes, such as methylene blue (MB) and neutral red. By successfully integrating the BiOCl ultrathin nanosheet/MB/H2O color switching system with poly(vinyl alcohol) hydrogel to fabricate a twistable gel film and simultaneously solving the dye-leaching issue of the gel film in a water environment, we further demonstrate its application in a colorimetric oxygen indicator for food packaging, exhibiting high sensitivity to monitor oxygen leakage by the naked eye. We believe the work opens a new avenue for designing photoreductive semiconductor nanomaterials to enrich the PCSSs and their applications.

Surface-bound sacrificial electron donors in promoting photocatalytic reduction on titania nanocrystals.

Titania nanocrystals have been investigated for fast color switching through photocatalytic reduction of dyes and hexacyanometalate pigments. Here we reveal that direct binding of sacrificial electron donors (SEDs) to the surface of titania nanocrystals can significantly promote the charge transfer rate by more efficiently scavenging photogenerated holes and releasing more photogenerated electrons for reduction reactions. Using diethylene glycol (DEG) as an example, we show that its binding to the nanoparticle surface, which can be achieved either during or after the nanoparticle formation, greatly enhances the photocatalytic reduction in comparison with the case where free DEG molecules are simply added as external SEDs.

Fast Dual-Stimuli-Responsive Dynamic Surface Wrinkles with High Bistability for Smart Windows and Rewritable Optical Displays.

The dynamic dual-stimuli-responsive surface wrinkles on a bilayer film with high bistability are unattainable and attractive for the applications of smart windows and optical displays. Here, we report a new strategy in developing moisture and temperature dual-responsive surface wrinkles on the polyvinyl alcohol/polydimethylsiloxane (PVA/PDMS) bilayer film by rationally designing the modulus changes of the PVA skin layer upon moisture and temperature. By optimizing the thickness of the PVA layer to 4.5 µm, the as-prepared surface wrinkles show long-awaited properties, such as fast response time, excellent reversibility without degradation of optical contrast, and high light transmittance modulation, which greatly outperforms the reported surface wrinkles. Moreover, the surface wrinkles on the bilayer film remain highly bistable without additional energy consumption for more than five months in ambient room conditions both in the opaque and transparent states. These promising dual-stimuli-responsive surface wrinkles on bilayer films hold great promises for various applications triggered by moisture and temperature, such as smart windows and rewritable optical displays.

Dynamic Color-Switching of Plasmonic Nanoparticle Films.

The fast and reversible switching of plasmonic color holds great promise for many applications, while its realization has been mainly limited to solution phases, achieving solid-state plasmonic color-switching has remained a significant challenge owing to the lack of strategies in dynamically controlling the nanoparticle separation and their plasmonic coupling. Herein, we report a novel strategy to fabricate plasmonic color-switchable silver nanoparticle (AgNP) films. Using poly(acrylic acid) (PAA) as the capping ligand and sodium borate as the salt, the borate hydrolyzes rapidly in response to moisture and produces OH- ions, which subsequently deprotonate the PAA on AgNPs, change the surface charge, and enable reversible tuning of the plasmonic coupling among adjacent AgNPs to exhibit plasmonic color-switching. Such plasmonic films can be printed as high-resolution invisible patterns, which can be readily revealed with high contrast by exposure to trace amounts of water vapor.

Fast-Response Flexible Photochromic Gels for Self-Erasing Rewritable Media and Colorimetric Oxygen Indicator Applications.

Photoreversible color switching that can change colors with fast response and high stability is urgently desired in color-on-demand applications. Yet, developing such materials has long been a significant challenge. In this work, a strategy based on the integration of TiO2 nanoparticle (NP) photocatalytic color switching of redox dyes and poly(vinyl alcohol) gel matrix could produce robust and flexible photochromic gels (FPGs) that exhibit fast light-responsive time and high photoreversible stability. Benefited by the soft network structures and monomeric form of redox dyes in the FPG maintained by poly(vinyl alcohol) and ethylene glycol molecules, as well as enhanced photoreductive activity of TiO2 NPs modified by both surface ligands and oxygen vacancies, the FPG exhibits long photoreversible switching cycles (≥50 times), decoloration in a short period of less than 8 s upon UV illumination, and recoloration in 16 min in ambient air and rapidly in 140 s upon near-infrared light illumination. Consequently, the excellent photoreversible color switching of the FPGs is highly applicable as both self-erasing rewritable media and colorimetric oxygen indicators. We believe that the current systems represent a big step forward toward practical applications, such as time-sensitive information storage, colorimetric oxygen sensor, and potentially many other technologies.

Reversible Assembly and Dynamic Plasmonic Tuning of Ag Nanoparticles Enabled by Limited Ligand Protection.

Dynamic manipulation of optical properties through the reversible assembly of plasmonic nanoparticles offers great opportunities for practical applications in many fields. The previous success, however, has been limited to Au nanoparticles. Reversible assembly and plasmonic tuning of Ag nanoparticles (AgNPs) have remained a significant challenge due to difficulty in finding an appropriate surface agent that can effectively stabilize the particle surface and control their interactions. Here, we overcome the challenge by developing a limited-ligand-protection (LLP) strategy for introducing poly(acrylic acid) with precisely controlled coverage to the AgNP surface to not only sufficiently stabilize the nanoparticles but also enable effective control over the surface charge and particle interaction through pH variation. The as-synthesized AgNPs can be reversibly assembled and disassembled and accordingly display broadly tunable coupling of plasmonic properties. Compared to the Au-based system, the success in the reversible assembly of AgNPs represents a significant step toward practical applications such as colorimetric pressure sensing because they offer many advantages, including broader spectral tuning range, higher color contrast, a one-pot process, and low materials and production cost. This work also highlights LLP as a new avenue for controlling the interparticle forces, their reversible assembly, and dynamic coupling of physical properties.