Non-discriminating engineered masking of immuno-evasive ligands on tumour-derived extracellular vesicles enhances tumour vaccination outcomes.

The success of personalized cancer immunotherapy depends on the initial tumour antigenic presentation to dendritic cells and macrophages. Tumour-derived extracellular vesicles (TEVs) contain abundant tumour antigenic molecules. The presence of anti-phagocytotic signals such as cluster of differentiation 47 (CD47) on the surface of the TEVs, however, leads to evasion of the same dendritic cells and macrophages. Here we show that iron oxide hydroxide nanocomposites can successfully mask TEV surfaces and unblock phagocytosis without affecting extracellular vesicles' elicited immune goals. After internalization, the mask disintegrates in the lysosome, releasing the tumour antigenic cargo. This triggers antigen presentation and promotes dendritic cell activation and maturation and macrophage reprogramming in animal models, leading to a drastic reduction of tumour volume and metastasis, and in human malignant pleural effusion clinical samples. This straightforward masking strategy eliminates the ubiquitous anti-phagocytosis block found in clinical samples and can be applied universally across all patient-specific TEVs as tumour antigenic agents for enhanced immunotherapy.

Selection of trophoblast cell surface antigen 2-targeted aptamer for the development of cytotoxic aptamer-drug conjugate.

Trophoblast cell surface antigen 2 expressed in several malignant cancers promotes tumor growth and metastasis via several signal transduction pathways. Trop2 is reputed as a prospective biomarker and therapeutic target. Trophoblast cell surface antigen 2-targeted agents, including antibodies, antibody conjugates and therapeutic combinations, could be utilized to fight cancers. To develop an effective drug targeting strategy, we resorted to a new trophoblast cell surface antigen 2-targeted anticancer treatment through aptamer conjugated with chemotherapeutic drug. This study identified trophoblast cell surface antigen 2-specific ssDNA aptamers using engineered trophoblast cell surface antigen 2 overexpression cells for cell-SELEX. The obtained ssDNA aptamer bound to trophoblast cell surface antigen 2 overexpressed cells with nanomolar affinity and was specific for several tumor cell types which express trophoblast cell surface antigen 2 abundantly. Significant cytotoxicity against HT29 cell by the conjugate of trophoblast cell surface antigen 2 aptamer and Emtansine was observed while resulting negligible therapeutic effect on human normal intestinal epithelial cell line HIEC in vitro, indicating that the conjugate shows potential as a promising therapeutic agent. Furthermore, the isolated aptamer demonstrated the ability for the targeted delivery, resulting excellent therapeutic effectiveness of aptamer-drug conjugate for xenograft tumor model of mice with human colorectal cancer.

Prolonged, staged, and self-regulated methotrexate release coupled with ROS scavenging in an injectable hydrogel for rheumatoid arthritis therapy.

Rheumatoid arthritis (RA) remains a formidable healthcare challenge due to its chronic nature and potential for irreversible joint damage. Methotrexate (MTX) is a cornerstone treatment for RA but carries significant risks of adverse effects with repeated administration, necessitating the exploration of alternative delivery methods. Injectable hydrogels loaded with MTX for intra-articular injection present a promising solution, allowing sustained drug release directly into affected joints. However, current hydrogel systems often lack extended therapeutic periods and the ability to self-regulate drug release according to disease state. Furthermore, RA is associated with excessive production of reactive oxygen species (ROS), which exacerbates inflammation and joint damage. Herein, we developed an advanced injectable hydrogel (MPDANPs/MTX HA-PEG gel) based on "bio-orthogonal chemistry", combining hyaluronic acid and polyethylene glycol (PEG) matrices co-loaded with mesoporous polydopamine nanoparticles (MPDANPs) and MTX. MPDANPs/MTX HA-PEG gel achieved prolonged, staged, and self-regulated MTX release, coupled with ROS scavenging capabilities for enhanced therapeutic efficacy. Due to its optimized MTX release behavior and significant ROS scavenging function, MPDANPs/MTX HA-PEG gel exhibited potent anti-inflammatory effects in collagen-induced arthritis (CIA) rats following a single intra-articular injection. Our findings highlight the potential of MPDANPs/MTX HA-PEG gel as a highly effective treatment strategy for RA, offering a promising avenue for improving patient outcomes.

Deciphering the Temporal-Spatial Interactive Heterogeneity of Long Non-Coding RNAs and RNA-Binding Proteins in Living Cells at Single-Cell Resolution.

The investigation of long noncoding RNAs (lncRNAs) and RNA binding proteins (RBPs) interactions in living cell holds great significance for elucidating their critical roles in a variety of biological activities, but limited techniques are available to profile the temporal-spatial dynamic heterogeneity. Here, we introduced a molecular beacon-functionalized nanoneedle array designed for spatially resolved profiling of lncRNA-RBP interactions (Nano-SpatiaLR). A nanoneedle array modified with a molecular beacon is employed to selectively isolate specific intracellular lncRNAs and their associated RBPs without affecting cell viability. The RBPs are then in situ analyzed with a fluorescent labeled antibody and colocalized with lncRNA signals to get a quantitative measurement of their dynamic interactions. Additionally, leveraging the spatial distribution and nanoscale modality of the nanoneedle array, this technique provides the spatial heterogeneity information on cellular lncRNA-RBPs interaction at single cell resolution. In this study, we tracked the temporal-spatial interactive heterogeneity dynamics of lncRNA-RBPs interaction within living cells across different biological progresses. Our findings demonstrated that the interactions between lncRNA HOTAIR and RBPs EZH2 and LSD1 undergo significant changes in response to drug treatments, particularly in tumor cells. Moreover, these interactions become more intensified as tumor cells aggregate during the proliferation process.

A "Dual-Key-and-Lock" MRI Contrast Agent with T1-T2 Switchable Function for Accurate Diagnosis of Tumors.

Extremely small iron oxide nanoparticle (ESIONP)-based stimuli-responsive switchable MRI contrast agents (CAs) show great promise for accurate detection of tumors due to their outstanding advantages of high specificity and low background signal. However, currently developed ESIONP-based switchable CAs often suffer single-biomarker-induced responses, which lack absolute specificity to pathological tissues, potentially diminishing diagnostic accuracy. In this study, weak acidity and hypoxia, two of the most remarkable characteristics of tumors, are introduced as dual biomarker stimuli to construct an ESIONP-based switchable MRI CA (DKL-CA), with its signal switch controlled by a "dual-key-and-lock" strategy. Only when DKL-CA is exposed to a coexisting weakly acidic and hypoxic environment can monodispersed ESIONPs form nanoclusters, thereby realizing a switch from the T1 to T2 contrast. Moreover, DKL-CA exhibits favorable biosafety and the capacity for precise tumor diagnosis in tumor-bearing mice. Overall, DKL-CA paves the way for designing highly accurate ESIONP-based MRI CAs for tumor diagnosis.

Flexible bidirectional self-powered photodetector with significantly reduced volume and accelerated response speed based on hydrogel and lift-off GaN-based nanowires.

Due to the wide range of potential applications for next-generation multi-functional devices, the flexible self-powered photodetector (PD) with polarity-switchable behavior is essential but very challenging to be realized. Herein, a wearable bidirectional self-powered PD based on detached (Al,Ga)N and (In,Ga)N nanowires has been proposed and demonstrated successfully. Arising from the photovoltage-competing dynamics across (Al,Ga)N and (In,Ga)N nanowire photoelectrodes, such PD can generate the positive (33.3 mA W -1) and negative (-0.019 mA W -1) photo-responsivity under ultraviolet (UV) and visible illumination, respectively, leading to the bidirectional photocurrent behavior. Thanks to the introduction of quasi solid-state hydrogel, the PD can work without the liquid-electrolyte, thus remarkably reducing the volume from about 482 cm3 to only 0.18 cm3. Furthermore, the use of hydrogel is found to enhance response speed in the UV range by reducing the response time for more than 95%, which is mainly attributed to the increased open circuit potential and reduced ion transport distance. As the GaN connecting segment is pretty thin, the piezoelectric charges generated by stress are proposed to have only a limited effect on the photocurrent density. Therefore, both the stable on-off switching characteristics and photocurrent densities can still be achieved after being bent 400 times. With an excellent flexibility, this work creates opportunities for technological applications of bidirectional photocurrent PDs in flexible optoelectronic devices, e.g., wearable intelligent sensors.

An Injectable Hydrogel Composing Anti-Inflammatory and Osteogenic Therapy toward Bone Erosions Microenvironment Remodeling in Rheumatoid Arthritis.

Healing bone erosions in rheumatoid arthritis (RA) remains greatly challenging via biomaterial strategies. Given the unsuccessful innate bone erosion healing due to an inflammatory disorder, over-activated osteoclasts, and impaired osteoblasts differentiation, RA pathogenesis-guided engineering of an innovative hydrogel platform is needed for remodeling osteoimmune and osteogenic microenvironment of bone erosion healing. Herein, in situ adaptable and injectable interpenetrating polymer network (IPN) hydrogel is developed through an ingenious combination of a bio-orthogonal reaction between hyaluronic acid (HA) and collagen, along with effective electrostatic interactions leveraging bisphosphonate (BP)-functionalized HA macromers (HABP) and nanorod shaped zinc (Zn)-doped biphasic calcium phosphate (ZnBCP). IPN hydrogel exhibits exceptional adaptability to the local shape complexity at bone erosions, and by integrating ZnBCP and HABP, a multi-stage releasing platform is engineered, facilitating controlled cargo delivery for remodeling more anti-inflammatory M2 cells and reducing over-activated osteoclastic activities, thereby reconstructing the bone regeneration microenvironment. Sustainedly co-delivering multiple ions (calcium and phosphate) can display excellent osteogenic properties and be conducive to the bone formation process, by effects of osteogenesis-associated cell differentiation. Overall, the introduced bioactive IPN hydrogel therapy remodels the osteoimmune environment by synergistic pro-inflammation-resolving, osteogenesis, and anti-osteoclastic activities, displaying excellent bone reconstruction in the collagen-induced arthritis rabbit model.

A responsive nanoplatform with molecular and structural imaging capacity for assisting accurate diagnosis of early rheumatoid arthritis.

Accurate early diagnosis of rheumatoid arthritis (RA) and prompt implementation of appropriate treatment approaches are crucial. In the clinic, magnetic resonance imaging (MRI) has been recommended for implementation to aid in the precise and early diagnosis of RA. However, they are still limited by issues regarding specificity and their ability to capture comprehensive information about the pathological features. Herein, a responsive multifunctional nanoplatform with targeting capabilities (hMnO2-IR@BSA-PEG-FA) is constructed through integrating a RA microenvironment-responsive MRI contrast agent with activatable near-infrared (NIR) fluorescence imaging, aiming to simultaneously acquire comprehensive pathological features of RA from both structural and molecular imaging perspectives. Moreover, taking advantage of its targeting function to synovial microphages, hMnO2-IR@BSA-PEG-FA demonstrated a remarkable capability to accumulate effectively at the synovial tissue. Additionally, hMnO2 responded to the mild acidity and reactive oxygen species (ROS) in the RA microenvironment, leading to the controlled release of Mn2+ ions and IR780, which separately caused special MRI contrast enhancement of synovial tissues and sensitively demonstrated the presence of ROS and weakly acid microenvironment by NIR imaging. Consequently, hMnO2-IR@BSA-PEG-FA is expected to serve as a promising nanoplatform, offering valuable assistance in the precise diagnosis of early-stage RA by specially providing comprehensive information about the pathological features.

Naturally biocompatible melanin based iron-complex nanoparticles for pH-responsive magnetic resonance imaging.

The sensitivity and diagnostic accuracy of magnetic resonance imaging mainly depend on the relaxation capacity of contrast agents (CAs) and their accumulated amount at the pathological region. Due to the better biocompatibility and high-spin capacity, Fe-complexes have been studied widely as an alternative to replace popular Gd-based CAs associated with potential biotoxicity. Compared with a variety of Fe complex-based CAs, such as small molecular, macrocyclic, multinuclear complexes, the form of nanoparticle exhibits outstanding longitudinal relaxation, but the clinical transformation was still limited by the inconspicuous difference of contrast between tumor and normal tissue. The enhanced effect of contrast is a positive relation as relaxation of CAs and their concentration in desired region. To specifically improve the amount of CAs accumulated in the tumor, pH-responsive polymer poly(2-ethyl-2-oxazoline) (PEOz) was modified on melanin, a ubiquitous natural pigment providing much active sites for chelating with Fe(III). The Fe(III)-Mel-PEOz we prepared could raise the tumor cell endocytosis efficiency via switching surface charge from anion to cation with the stimuli of the decreasing pH of tumor microenvironment. The change of pH has negligible effect on ther1of Fe(III)-Mel-PEOz, which is always maintained at around 1.0 mM-1s-1at 0.5 T. Moreover, Fe(III)-Mel-PEOz exhibited low cytotoxicity, and satisfactory enhancement of positive contrast effectin vivo. The excellent biocompatibility and stable relaxation demonstrate the high potential of Fe(III)-Mel-PEOz in the diagnosis of tumor.

An Engineered Nanoplatform with Tropism Toward Irradiated Glioblastoma Augments Its Radioimmunotherapy Efficacy.

Combining radiotherapy with immune checkpoint blockade therapy offers a promising approach to treat glioblastoma multiforme (GBM), yet challenges such as limited effectiveness and immune-related adverse events (irAEs) persist. These issues are largely due to the failure in targeting immunomodulators directly to the tumor microenvironment. To address this, a biomimetic nanoplatform that combines a genetically modified mesenchymal stem cell (MSC) membrane with a bioactive nanoparticle core for chemokine-directed radioimmunotherapy of GBM is developed. The CC chemokine receptor 2 (CCR2)-overexpressing MSC membrane acts as a tactical tentacle to achieve radiation-induced tropism toward the abundant chemokine (CC motif) ligand 2 (CCL2) in irradiated gliomas. The nanoparticle core, comprising diselenide-bridged mesoporous silica nanoparticles (MSNs) and PD-L1 antibodies (αPD-L1), enables X-ray-responsive drug release and radiosensitization. In two murine models with orthotopic GBM tumors, this nanoplatform reinvigorated immunogenic cell death, and augmented the efficacy and specificity of GBM radioimmunotherapy, with reduced occurrence of irAEs. This study suggests a promising radiation-induced tropism strategy for targeted drug delivery, and presents a potent nanoplatform that enhances the efficacy and safety of radio-immunotherapy.

Advances in conductive hydrogels for neural recording and stimulation.

The brain-computer interface (BCI) allows the human or animal brain to directly interact with the external environment through the neural interfaces, thus playing the role of monitoring, protecting, improving/restoring, enhancing, and replacing. Recording electrophysiological information such as brain neural signals is of great importance in health monitoring and disease diagnosis. According to the electrode position, it can be divided into non-implantable, semi-implantable, and implantable. Among them, implantable neural electrodes can obtain the highest-quality electrophysiological information, so they have the most promising application. However, due to the chemo-mechanical mismatch between devices and tissues, the adverse foreign body response and performance loss over time seriously restrict the development and application of implantable neural electrodes. Given the challenges, conductive hydrogel-based neural electrodes have recently attracted much attention, owing to many advantages such as good mechanical match with the native tissues, negligible foreign body response, and minimal signal attenuation. This review mainly focuses on the current development of conductive hydrogels as a biocompatible framework for neural tissue and conductivity-supporting substrates for the transmission of electrical signals of neural tissue to speed up electrical regeneration and their applications in neural sensing and recording as well as stimulation.

Implantable Neural Microelectrodes: How to Reduce Immune Response.

Implantable neural microelectrodes exhibit the great ability to accurately capture the electrophysiological signals from individual neurons with exceptional submillisecond precision, holding tremendous potential for advancing brain science research, as well as offering promising avenues for neurological disease therapy. Although significant advancements have been made in the channel and density of implantable neural microelectrodes, challenges persist in extending the stable recording duration of these microelectrodes. The enduring stability of implanted electrode signals is primarily influenced by the chronic immune response triggered by the slight movement of the electrode within the neural tissue. The intensity of this immune response increases with a higher bending stiffness of the electrode. This Review thoroughly analyzes the sequential reactions evoked by implanted electrodes in the brain and highlights strategies aimed at mitigating chronic immune responses. Minimizing immune response mainly includes designing the microelectrode structure, selecting flexible materials, surface modification, and controlling drug release. The purpose of this paper is to provide valuable references and ideas for reducing the immune response of implantable neural microelectrodes and stimulate their further exploration in the field of brain science.

Tumor microenvironment reprogramming combined with immunogenic enhancement by nanoemulsions potentiates immunotherapy.

The combination of immune checkpoint inhibitors and immunogenic cell death (ICD) inducers has become a promising strategy for the treatment of various cancers. However, its efficacy remains unmet because of the dense stroma and defective vasculatures in the tumor microenvironment (TME) that restricts the intratumoral infiltration of cytotoxic T lymphocytes (CTLs). Herein, cancer-associated fibroblasts (CAFs)-targeted nanoemulsions are tailored to combine the ICD induction and the TME reprogramming to sensitize checkpoint blockade immunotherapy. Melittin, as an ICD inducer and an antifibrotic agent, is efficiently encapsulated into the nanoemulsion accompanied by a nitric oxide donor to improve its bioavailability and tumor targeting. The nanoemulsions exhibited dual functionality by directly inducing direct cancer cell death and enhancing the tumoral immunogenicity, while also synergistically reprogramming the TME through reversing the activated CAFs, decreasing collagen deposition and restoring tumor vessels. Consequently, these nanemulsions successfully facilitated the CTLs infiltration and suppressing the recruitment of immunosuppressive cells. A combination of AE-MGNPs and anti-CTLA-4 antibody greatly elicited a striking level of antitumor T-cell response to suppress tumor growth in CAFs-rich colorectal tumor models. Our work emphasized the integration of the ICD induction with simultaneous modulation of the TME to enhance the sensitivity of patients to checkpoint blockade immunotherapy.

Flexible light-stimulated artificial synapse based on detached (In,Ga)N thin film for neuromorphic computing.

Because of wide range of applications, the flexible artificial synapse is an indispensable part for next-generation neural morphology computing. In this work, we demonstrate a flexible synaptic device based on a lift-off (In,Ga)N thin film successfully. The synaptic device can mimic the learning, forgetting, and relearning functions of biological synapses at both flat and bent states. Furthermore, the synaptic device can simulate the transition from short-term memory to long-term memory successfully under different bending conditions. With the high flexibility, the excitatory post-synaptic current of the bent device only shows a slight decrease, leading to the high stability. Based on the experimental conductance for long-term potentiation and depression, the simulated three-layer neural network can achieve a high recognition rate up to 90.2%, indicating that the system comprising of flexible synaptic devices could have a strong learning-memory capability. Therefore, this work has a great potential for the development of wearable intelligence devices and flexible neuromorphic systems.

Flexible Monolithic Bifunctional Device Based on a Lift-off (In,Ga)N Film for Both Lighting and Self-Driven Detection.

Although flexible monolithic bifunctional devices are significant for next-generation optoelectronic devices, it is quite challenging to realize them. In this work, a flexible monolithic device with both functions of emission and self-driven detection has been proposed and demonstrated successfully. By a quick electrochemical etching method, the device is created using a lift-off (In,Ga)N film detaching from the epitaxial silicon substrate. The Si removal is beneficial for releasing stress and reducing the internal polarization effects under bending conditions, keeping the electroluminescence peak wavelength quite stable. With good flexibility, the monolithic bifunctional device can maintain both stable detection and emission performance under bending conditions. Furthermore, two functions of detection and lighting of the flexible monolithic device can not only be realized separately but also simultaneously. This means that the flexible monolithic device can detect and emit light at the same time. With the advantages of miniaturization and multifunctionality, this work paves an effective way to develop new monolithic multifunctional devices for both self-driven detection and wearable intelligent display.

Hierarchical integration of DNA nanostructures and NanoGold onto a microchip facilitates covalent chemistry-mediated purification of circulating tumor cells in head and neck squamous cell carcinoma.

It is well-established that the combined use of nanostructured substrates and immunoaffinity agents can enhance the cell-capture performance of the substrates, thus offering a practical solution to effectively capture circulating tumor cells (CTCs) in peripheral blood. Developing along this strategy, this study first demonstrated a top-down approach for the fabrication of tetrahedral DNA nanostructure (TDN)-NanoGold substrates through the hierarchical integration of three functional constituents at various length-scales: a macroscale glass slide, sub-microscale self-organized NanoGold, and nanoscale self-assembled TDN. The TDN-NanoGold substrates were then assembled with microfluidic chaotic mixers to give TDN-NanoGold Click Chips. In conjunction with the use of copper (Cu)-catalyzed azide-alkyne cycloaddition (CuAAC)-mediated CTC capture and restriction enzyme-triggered CTC release, TDN-NanoGold Click Chips allow for effective enumeration and purification of CTCs with intact cell morphologies and preserved molecular integrity. To evaluate the clinical utility of TDN-NanoGold Click Chips, we used these devices to isolate and purify CTCs from patients with human papillomavirus (HPV)-positive (+) head and neck squamous cell carcinoma (HNSCC). The purified HPV(+) HNSCC CTCs were then subjected to RT-ddPCR testing, allowing for detection of E6/E7 oncogenes, the characteristic molecular signatures of HPV(+) HNSCC. We found that the resulting HPV(+) HNSCC CTC counts and E6/E7 transcript copy numbers are correlated with the treatment responses in the patients, suggesting the potential clinical utility of TDN-NanoGold Click Chips for non-invasive diagnostic applications of HPV(+) HNSCC.

Engineering GaN/AuNC core-shell nanowire heterojunctions by gold nanoclusters with excitation-dependent behavior for enhancing the responsivity and stability of self-driven photodetectors.

Self-driven broadband photodetectors (PDs) with low-power consumption have great potential applications in the wide range of next-generation optoelectronic devices. In this study, a self-driven broadband PD responding to an ultraviolet-visible range based on gallium nitride/gold nanocluster (GaN/AuNC) core-shell nanowire heterojunctions is fabricated for the first time. By introducing the AuNCs onto the GaN nanowire surfaces, the GaN/AuNC core-shell nanowire heterojunctions can be formed efficiently. It is crucial that AuNCs have the functions of light collectors and hole conductors in heterojunctions due to the suitable energy level alignment. Under the optimized conditions of AuNCs, it is found that GaN/AuNC core-shell nanowires can significantly increase the photocurrent and responsivity of PDs, mainly resulting from the light interreflection within the heterojunctions and the effective improvement of carrier transport. Owing to the excitation-dependent emission behavior of AuNCs, the responsivity of PD with GaN/AuNC core-shell nanowire heterojunctions can be enhanced by around 330% compared with that of PD without AuNCs under visible illumination. Furthermore, GaN/AuNC hybrid nanowires with excitation-dependent fluorescence behavior can modulate the enhanced amplitude performance of broadband PDs. Owing to the high stability of AuNCs, the photocurrent of the PD with AuNCs is still quite stable after continuous operation for more than 20 000 s. Therefore, this study provides an effective method for developing new broadband PDs with high performance and low energy consumption.

Donor-Acceptor Engineering for Tailoring Highly Efficient Photosensitizers for Image-Guided Antitumor Photodynamic Therapy.

Photosensitizers (PSs) have greatly flourished as a promising tool for photodynamic therapy owing to their integration of both in situ diagnosis and treatment in a single nanoplatform. However, there is still a need to explore synthesis pathways that can result in high-performance PSs with good reproducibility, high yield, less dark toxicity, and an attractive therapeutic index. Therefore, by exploiting the precise molecular engineering guideline, this work unveils a straightforward protocol to fabricate three homologous PSs (TPA-T-RS, TPA-Ts-RS, and TPA-Ts-RCN) with aggregation-induced emission (AIE) characteristics. Through slight structural tuning, the PSs are capable of anchoring to the cell membrane, mitochondria, and lysosome, and effectively generating reactive oxygen species (ROS). More importantly, TPA-Ts-RCN proved an intuitively appealing imaging-guided photodynamic therapy (PDT) effect. This work is expected to add a promising dimension to the field of architecting AIE PSs for image-guided photodynamic therapy.

A metal-organic framework complex for enhancing tumor treatments through synergistic effect of chemotherapy and photodynamic therapy.

Porphyrin-based metal-organic frameworks (PMOFs) are a kind of crystal hybrid material with broad application prospects in energy, catalysis, biomedicine, and other fields. In this study, the La-TCPP PMOF nanocrystal was constructed using a porphyrin ligand and La ion. This material can produce a high loading rate on doxorubicin (DOX) owing to its special porous structure. The high loading rate of drug molecules and the reactive oxygen species (ROS) of the porphyrin ligand enable La-TCPP@DOX nanocrystal to produce a powerful killing effect on cancer cells under the synergistic attack of chemotherapy (CT) and photodynamic therapy (PDT). Finally, by modifying the targeted aptamer, the actual therapeutic effect of this special La-TCPP@DOX@Apt material on tumors was confirmed by applying the established mouse tumor model. The composite nanomaterial not only avoids the side effects caused by high concentrations of chemotherapeutic drugs, but also overcomes the limitation of PDT owing to insufficient light penetration and can inhibit and kill solid tumors under the condition of synergistic attack. This study is a complement to PMOF crystal materials, and its tumor-killing ability was achieved by loading drugs and introducing targeting molecules, which proves that the synergistic attack can more effectively inhibit and treat solid tumors. These studies have a reference and guiding significance for the treatment of cancer patients.

MMP-Responsive Nanoparticle-Loaded, Injectable, Adhesive, Self-Healing Hydrogel Wound Dressing Based on Dynamic Covalent Bonds.

Developing a multifunctional hydrogel wound dressing with good injectability, self-healing, tissue adhesion, biocompatibility, and fast skin wound healing efficiency remains challenging. In this work, an injectable adhesive dopamine-functionalized oxidized hyaluronic acid/carboxymethyl chitosan/collagen (AHADA/CCS/Col) hydrogel was constructed. The Schiff dynamic bond between AHADA and CCS, the N-Ag-N bond between CCS and Ag ions, and the S-Ag-S dynamic bond between sulfhydryl-modified collagen (ColSH) and Ag ions allowed the hydrogel to be both injectable and self-healing. Moreover, the aldehyde groups and catechol groups presented in the hydrogel could generate force with several groups on the tissue interface; therefore, the hydrogel also had good tissue adhesion. In vitro experiments proved that this hydrogel exhibited good biocompatibility and could promote cell proliferation. Additionally, curcumin (Cur)-loaded gelatin nanoparticles (Cur@Gel NPs) were prepared, which could respond to matrix metalloproteinases (MMPs) and controllably release Cur to hasten wound healing efficiency. Animal experiment results showed that this AHADA/CCS/Col hydrogel loaded with Cur@Gel NPs promoted wound repairing better, indicating its potential as a wound dressing.