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As known, the benefits of photothermal therapy (PTT) are greatly limited by the heat tolerance of cancer cells resulting from overexpressed heat shock proteins (HSPs). Then HSPs further trigger the formation of stress granules (SGs) that regulate protein expression and cell viability under various stress conditions. Inhibition of SG formation can sensitize tumor cells to PTT. Herein, we developed PEGylated pH (low) insertion peptide (PEG-pHLIP)-modified hollow copper sulfide nanoparticles (HCuS NPs) encapsulating the SG inhibitor ISRIB, with the phase-change material lauric acid (LA) as a gate-keeper, to construct a pH-driven and NIR photo-responsive controlled smart drug delivery system (IL@H-PP). The nanomedicine could specifically target slightly acidic tumor sites. Upon irradiation, IL@H-PP realized PTT, and the light-controlled release of ISRIB could effectively inhibit the formation of PTT-induced SG to sensitize tumor cells to PTT, thereby increasing the antitumor effect and inducing potent immunogenic cell death (ICD). Moreover, IL@H-PP could promote the production of reactive oxygen species (ROS) by tumor-associated macrophages (TAMs), repolarizing them towards the M1 phenotype and remodeling the immunosuppressive microenvironment. In vitro/vivo results revealed the potential of PTT combined with SG inhibitors, which provides a new paradigm for antitumor and anti-metastases.

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The non-fouling condition, bacteria-free environment and suitable moisture at wound site are crucial for chronic wound healing. However, it remains highly meaningful yet challenging to develop wound dressings that can simultaneously achieve these desirable functions. In this work, a kind of multifunctional Janus polyurethane sponge (Janus-PU) was designed and fabricated by coating near-infrared (NIR)-responsive and superhydrophobic nanoparticles (F-ZnO@Ag NPs) on one surface of sponge. The nano-functionalized outer layer can endow Janus-PU with superhydrophobic antifouling property for preventing bacterial colonization and broad-spectrum antibacterial activity due to the presence of Ag NPs. Especially, the synergistic combination of asymmetric structure and strong NIR photothermal effect can impart Janus-PU with NIR-controlled unidirectional exudate removal, thus achieving an optimal wetting environment for wound healing. The mice full-thickness skin acute wounds treated with Janus-PU under NIR irradiation showed superior anti-infection and healing effect compared to the commercial dressings. Significantly, the treatment using Janus-PU with NIR irradiation can accelerate the recovery of methicillin-resistant Staphylococcus aureus (MRSA)-infected diabetic chronic wounds due to the synergistic effect of antibiofouling, antibacterial and exudate-managing. The Janus-PU as a promising multifunctional dressing can prevent bacterial invasion and create an appropriate environment for wound healing, providing an effective solution for intractable wounds and infections. STATEMENT OF SIGNIFICANCE: The development of advanced wound dressings to ensure non-fouling condition, bacteria-free environment and suitable moisture is crucial for chronic wound healing. However, it remains a considerable challenge to simultaneously integrate antibiofouling, antibacterial and exudate-managing properties into a single dressing. In this work, we developed a kind of multifunctional Janus polyurethane sponge (Janus-PU) by a single-sided superhydrophobic modification strategy, which can simultaneously achieve superhydrophobic antifouling property, effective broad-spectrum antibacterial and near-infrared controlled exudate removal. The Janus-PU designed herein can not only create an optimal environment for accelerated wound healing, but also avoid frequent dressing replacement, thus providing an ideal material system for intractable wounds and infections.

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The treatment for diabetic ulcers still remains a big clinic challenge owing to the adverse repair microenvironment. Bioactive glasses (BGs) play an important role in the late stages of healing due to their ability to promote vascularization and collagen fiber deposition, but fail to improve infection and oxidative stress in the early stage.Therefore, it is critical to develop a material involved in regulating the whole healing phases. In this work, BGs-based nanozymes (MnO2 @PDA-BGs) with antioxidation, antibacterial and pro-healing abilities are synthesized by the redox deposition of MnO2 on mesoporous BGs. Afterward, cryogel with the interconnected macropore structure is fabricated by the polymerization of methacrylate anhydride gelatin (GelMA) at -20 °C. MnO2 @PDA-BGs are loaded into the cryogel to obtain nanocomposite cryogel (MnO2 @PDA-BGs/Gel) with multiple enzymes-like- activities to eliminate reactive oxygen species (ROS). Besides, MnO2 @PDA-BGs/Gel has intensive peroxidase-like activity under acidic condition and near infrared photothermal responsiveness to achieve excellent antibacterial performance. Cells experiments demonstrate that MnO2 @PDA-BGs/Gel recruits L929s and promotes their proliferation. Furthermore, MnO2 @PDA-BGs/Gel eliminates intracellular overexpressed ROS and maintains the viability of L929s. Animal experiments confirm that MnO2 @PDA-BGs/Gel promotes wound healing and avoided scarring by killing bacteria, reversing inflammation, promoting vascularization, and improving the deposition of collagen III.

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Bacterial infection, excessive inflammation and damaging blood vessels network are the major factors to delay the healing of diabetic ulcer. At present, most of wound repair materials are passive and can't response to the wound microenvironment, resulting in a low utilization of bioactive substances and hence a poor therapeutic effect. Therefore, it's essential to design an intelligent wound dressing responsive to the wound microenvironment to achieve the release of drugs on-demand on the basis of multifunctionality. In this work, metformin-laden CuPDA NPs composite hydrogel (Met@ CuPDA NPs/HG) was fabricated by dynamic phenylborate bonding of gelatin modified by dopamine (Gel-DA), Cu-loaded polydopamine nanoparticles (CuPDA NPs) with hyaluronic acid modified by phenyl boronate acid (HA-PBA), which possessed good injectability, self-healing, adhesive and DPPH scavenging performance. The slow release of metformin was achieved by the interaction with CuPDA NPs, boric groups (B-N coordination) and the constraint of hydrogel network. Metformin had a pH and glucose responsive release behavior to treat different wound microenvironment intelligently. Moreover, CuPDA NPs endowed the hydrogel excellent photothermal responsiveness to kill bacteria of >95% within 10 min and also the slow release of Cu2+ to protect wound from infection for a long time. Met@ CuPDA NPs/HG also recruited cells to a certain direction and promoted vascularization by releasing Cu2+. More importantly, Met@CuPDA NPs/HG effectively decreased the inflammation by eliminating ROS and inhibiting the activation of NF-κB pathway. Animal experiments demonstrated that Met@CuPDA NPs/HG significantly promoted wound healing of diabetic SD rats by killing bacteria, inhibiting inflammation, improving angiogenesis and accelerating the deposition of ECM and collagen. Therefore, Met@CuPDA NPs/HG had a great application potential for diabetic wound healing.

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As known, the benefits of photothermal therapy (PTT) are greatly limited by the heat tolerance of cancer cells resulting from overexpressed heat shock proteins (HSPs). Then HSPs further trigger the formation of stress granules (SGs) that regulate protein expression and cell viability under various stress conditions. Inhibition of SG formation can sensitize tumor cells to PTT. Herein, we developed PEGylated pH (low) insertion peptide (PEG-pHLIP)-modified hollow copper sulfide nanoparticles (HCuS NPs) encapsulating the SG inhibitor ISRIB, with the phase-change material lauric acid (LA) as a gate-keeper, to construct a pH-driven and NIR photo-responsive controlled smart drug delivery system (IL@H-PP). The nanomedicine could specifically target slightly acidic tumor sites. Upon irradiation, IL@H-PP realized PTT, and the light-controlled release of ISRIB could effectively inhibit the formation of PTT-induced SG to sensitize tumor cells to PTT, thereby increasing the antitumor effect and inducing potent immunogenic cell death (ICD). Moreover, IL@H-PP could promote the production of reactive oxygen species (ROS) by tumor-associated macrophages (TAMs), repolarizing them towards the M1 phenotype and remodeling the immunosuppressive microenvironment. In vitro/vivo results revealed the potential of PTT combined with SG inhibitors, which provides a new paradigm for antitumor and anti-metastases.

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Stimulus-responsive hydrogels are an important member of smart materials owing to their reversibility, soft/wet properties, and biocompatibility, which have a wide range of applications in the field of intelligent actuations. However, poor mechanical property and complicated fabrication process limit their further applications. Herein, we report a light-responsive tissue paper/hydrogel composite actuator which was developed by combining inkjet-printed tissue paper with poly(N-isopropylacrylamide) (PNIPAM) hydrogel through simple in situ polymerization. Due to the high strength of natural tissue paper and the strong interaction within the interface of the bilayer structure, the mechanical property of the composite actuator was highly enhanced, reaching 1.2 MPa of tensile strength. Furthermore, the light-responsive actuation of remote manipulation can be achieved because of the stamping graphite with high efficiency of photothermal conversion. Most importantly, we also made a few remotely controlled biomimetic actuating devices based on the near-infrared (NIR) light response of this composite actuator. This work provides a simple strategy for the construction of biomimetic anisotropic actuators and will inspire the exploration of new intelligent materials.

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Tumor surgery is often accompanied by tumor residue, tissue defects, bleeding, and bacterial infection, which can easily cause tumor recurrence, low survival rates, and delay wound healing. In this study, a multifunctional hydrogel (CA-AuAgNPs-Gel) was developed to prevent tumor recurrence and promote wound healing after tumor surgery in the absence of chemotherapeutic drugs and antibiotics. CA-AuAgNPs-Gel was prepared using iota carrageenan (CA)-capped gold­silver nanoparticles (CA-AuAgNPs) and poloxamer 407 (F127), which exhibited good biocompatibility, injectability, and near-infrared (NIR) photothermal responsiveness. CA-AuAgNPs-Gel inhibited the growth of 4T1 breast cancer in situ and the recurrence of surgically resected B16F10 melanoma. It also effectively stopped bleeding and promoted tumor postsurgical wound healing in vivo. Importantly, CA-AuAgNPs-Gel induced tumor apoptosis via photothermal-induced hyperthermia and immunogenic cell death (ICD) under NIR laser radiation. Collectively, this hydrogel shows significant clinical application prospects for inhibiting tumor recurrence and promoting wound healing for postsurgical tumor treatment.

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Stimulus-responsive hydrogels are of great significance in soft robotics, wearable electronic devices, and sensors. Near-infrared (NIR) light is considered an ideal stimulus as it can trigger the response behavior remotely and precisely. In this work, a smart flexible stimuli-responsive hydrogel with excellent photothermal property and decent conductivity are prepared by incorporating MXene nanosheets into the physically cross-linked poly(N-isopropyl acrylamide) hydrogel matrix. Because of outstanding photothermal effect and dispersion of MXene, the composite hydrogel exhibits rapid photothermal responsiveness and excellent photothermal stability under the NIR irradiation. Furthermore, the anisotropic bilayer hydrogel actuator shows fast and controllable light-driven bending behavior, which can be used as a light-controlled soft manipulator. Meanwhile, the hydrogel sensor exhibits cycling stability and good durability in detecting various deformation and real-time human activities. Therefore, the present study involving the fabrication of MXene nanocomposite hydrogels for potential applications in remotely controlled actuator and wearable electronic device provides a new method for the development of photothermal responsive conductive hydrogels.

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The rapid development of intelligent technology and industry has induced higher requirements for multifunctional materials, especially intelligent materials with stimulus-responsive self-actuation behavior. In this study, a Cu@PVA-co-PE/GO composite actuation film, with an asymmetric sandwich structure, was prepared by attaching graphene oxide (GO) to the surface of a polyvinyl alcohol ethylene copolymer (PVA-co-PE) nanofiber composite film containing copper nanoparticles (Cu) through layer-on-layer adsorption. This unique structural design endowed the composite film with not only excellent structural stability but also different bending directions (in response to moisture and infrared light). The actuation performance shows that when the adsorption time was 4 h, the maximum bending angle of the Cu@PVA-co-PE/GO composite film was up to 90° within 5.99 s. Furthermore, the actuation behavior was stable after 100 cycles of reversible moisture stimulation. Additionally, the maximum actuation strain of the composite film was up to 1.35 MPa during the illumination time of 6.8 s and maintained an excellent stability for 400 s under continuous infrared stimulation of 0.53 W/cm2. The rapid and sensitive stimulus response of the Cu@PVA-co-PE/GO composite film exhibited self-actuation behavior under the remote control of moisture and infrared light. This, in turn, suggests prospects for wide applications in emerging technologies, such as intelligent switches, artificial muscles, intelligent medical treatment, and flexible robots.