PAD4 Inhibitor-Functionalized Layered Double Hydroxide Nanosheets for Synergistic Sonodynamic Therapy/Immunotherapy Of Tumor Metastasis.

Sonodynamic therapy (SDT) is demonstrated to trigger the systemic immune response of the organism and facilitate the treatment of metastatic tumors. However, SDT-mediated neutrophil extracellular traps (NETs) formation can promote tumor cell spread, thus weakening the therapeutic effectiveness of metastatic tumors. Herein, the amorphous CoW-layered double hydroxide (a-CoW-LDH) nanosheets are functionalized with a peptidyl arginine deiminase 4 (PAD4) inhibitor, i.e., YW3-56, to construct a multifunctional nanoagent (a-LDH@356) for synergistic SDT/immunotherapy. Specifically, a-CoW-LDH nanosheets can act as a sonosensitizer to generate abundant reactive oxygen species (ROS) under US irradiation. After loading with YW3-56, a-LDH@356 plus US irradiation not only effectively induces ROS generation and immunogenic cell death, but also inhibits the elevation of citrullinated histone H3 (H3cit) and the release of NETs, enabling a synergistic enhancement of anti-tumor metastasis effect. Using 4T1 tumor model, it is demonstrated that combining a-CoW-LDH with YW3-56 stimulates an anti-tumor response by upregulating the proportion of immune-activated cells and inducing polarization of M1 macrophages, and inhibits immune escape by downregulating the expression of PD-1 on immune cells under US irradiation, which not only arrests primary tumor progression with a tumor inhibition rate of 69.5% but also prevents tumor metastasis with the least number of lung metastatic nodules.

A MgAl-LDH-CuS nanosheet-based thermo-responsive composite hydrogel with nir-responsive angiogenesis inhibitor releasing capability for multimode starvation therapy.

The rapid proliferation of tumors is highly dependent on the nutrition supply of blood vessels. Cutting off the nutrient supply to tumors is an effective strategy for cancer treatment, known as starvation therapy. Although various hydrogel-based biomaterials have been developed for starvation therapy through glucose consumption or intravascular embolization, the limitations of single-mode starvation therapy hinder their therapeutic effects. Herein, we propose a dual-function nutrition deprivation strategy that can block the nutrients delivery through extravascular gelation shrinkage and inhibit neovascularization through angiogenesis inhibitors based on a novel NIR-responsive nanocomposite hydrogel. CuS nanodots-modified MgAl-LDH nanosheets loaded with angiogenesis inhibitor (sorafenib, SOR) are incorporated into the poly(n-isopropylacrylamide) (PNIPAAm) hydrogel by radical polymerization to obtain the composite hydrogel (SOR@LDH-CuS/P). The SOR@LDH-CuS/P hydrogel can deliver hydrophobic SOR with a NIR-responsive release behavior, which could decrease the tumor vascular density and accelerate cancer cells apoptosis. Moreover, the SOR@LDH-CuS/P hydrogel exhibits higher (3.5 times) compressive strength than that of the PNIPAAm, which could squeeze blood vessels through extravascular gelation shrinkage. In vitro and in vivo assays demonstrate that the interruption of nutrient supply by gelation shrinkage and the prevention of angiogenesis by SOR is a promising strategy to inhibit tumor growth for multimode starvation therapy.

Synergistic Interaction between Metal Single-Atoms and Defective WO3- x Nanosheets for Enhanced Sonodynamic Cancer Therapy.

Although metal single-atom (SA)-based nanomaterials are explored as sonosensitizers for sonodynamic therapy (SDT), they normally exhibit poor activities and need to combine with other therapeutic strategies. Herein, the deposition of metal SAs on oxygen vacancy (OV)-rich WO3- x nanosheets to generate a synergistic effect for efficient SDT is reported. Crystalline WO3 and OV-rich WO3- x nanosheets are first prepared by simple calcination of the WO3 ·H2 O nanosheets under an air and N2 atmosphere, respectively. Pt, Cu, Fe, Co, and Ni metal SAs are then deposited on WO3- x nanosheets to obtain metal SA-decorated WO3- x nanocomposites (M-WO3- x ). Importantly, the Cu-WO3- x sonosensitizer exhibits a much higher activity for ultrasound (US)-induced production of reactive oxygen species than that of the WO3- x and Cu SA-decorated WO3 , which is also higher than other M-WO3- x nanosheets. Both the experimental and theoretical results suggest that the excellent SDT performance of the Cu-WO3- x nanosheets should be attributed to the synergistic effect between Cu SAs and WO3- x OVs. Therefore, after polyethylene glycol modification, the Cu-WO3- x can quickly kill cancer cells in vitro and effectively eradicate tumors in vivo under US irradiation. Transcriptome sequencing analysis and further molecular validation suggest that the Cu-WO3- x -mediated SDT-activated apoptosis and TNF signaling pathways are potential drivers of tumor apoptosis induction.

Combined analysis of mRNA and miRNA transcriptomes reveals the regulatory mechanism of Xanthomonas arboricola pv pruni resistance in Prunus persica.

BACKGROUND: Peach bacterial shot hole, caused by Xanthomonas arboricola pv pruni (Xap), is a global bacterial disease that poses a threat to the yield and quality of cultivated peach trees (Prunus persica). RESULTS: This study compared the mRNA and miRNA profiles of two peach varieties, 'Yanbao' (resistant) and 'Yingzui' (susceptible), after inoculation with Xap to identify miRNAs and target genes associated with peach tree resistance. mRNA sequencing results revealed that in the S0-vs-S3 comparison group, 1574 genes were upregulated and 3975 genes were downregulated. In the R0-vs-R3 comparison group, 1575 genes were upregulated and 3726 genes were downregulated. Through miRNA sequencing, a total of 112 known miRNAs belonging to 70 miRNA families and 111 new miRNAs were identified. Notably, some miRNAs were exclusively expressed in either resistant or susceptible varieties. Additionally, 59 miRNAs were downregulated and 69 miRNAs were upregulated in the R0-vs-R3 comparison group, while 46 miRNAs were downregulated and 52 miRNAs were upregulated in the S0-vs-S3 comparison group. Joint analysis of mRNA and miRNA identified 79 relationship pairs in the S0-vs-S3 comparison group, consisting of 48 miRNAs and 51 target genes. In the R0-vs-R3 comparison group, there were 58 relationship pairs, comprising 28 miRNAs and 20 target genes. Several target genes related to resistance, such as SPL6, TIFY6B, and Prupe.4G041800_v2.0.a1 (PPO), were identified through literature reports and GO/KEGG enrichment analysis. CONCLUSION: In conclusion, this study discovered several candidate genes involved in peach tree resistance by analyzing differential expression of mRNA and miRNA. These findings provide valuable insights into the mechanisms underlying resistance to Xap in peach trees.

Catalyzing Generation and Stabilization of Oxygen Vacancies on CeO2-x Nanorods by Pt Nanoclusters as Nanozymes for Catalytic Therapy.

Although CeO2 nanomaterials have been widely explored as nanozymes for catalytic therapy, they still suffer from relatively low activities. Herein, the catalyzing generation and stabilization of oxygen vacancies on CeO2 nanorods by Pt nanoclusters via H2 gas reduction under mild temperature (350 °C) to obtain Pt/CeO2- x , which can serve as a highly efficient nanozyme for catalytic cancer therapy, is reported. The deposited Pt on CeO2 by the atomic layer deposition technique not only can serve as the catalyst to generate oxygen vacancies under mild temperature reduction through the hydrogen spillover effect, but also can stabilize the generated oxygen vacancies. Meanwhile, the oxygen vacancies also provide anchoring sites for Pt forming strong metal-support interactions and thus preventing their agglomerations. Importantly, the Pt/CeO2- x reduced at 350 °C (Pt/CeO2- x -350R) exhibits excellent enzyme-mimicking catalytic activity for generation of reactive oxygen species (e.g., ·OH) as compared to other control samples, including CeO2 , Pt/CeO2 , and Pt/CeO2- x reduced at other temperatures, thus achieving excellent performance for tumor-specific catalytic therapy to efficiently eliminate cancer cells in vitro and ablate tumors in vivo. The excellent enzyme-mimicking catalytic activity of Pt/CeO2- x -350R originates from the good catalytic activities of oxygen vacancy-rich CeO2- x and Pt nanoclusters.

Layered Double Hydroxides: A Novel Promising 2D Nanomaterial for Bone Diseases Treatment.

Bone diseases including bone defects, bone infections, osteoarthritis, and bone tumors seriously affect life quality of the patient and bring serious economic burdens to social health management, for which the current clinical treatments bear dissatisfactory therapeutic effects. Biomaterial-based strategies have been widely applied in the treatment of orthopedic diseases but are still plagued by deficient bioreactivity. With the development of nanotechnology, layered double hydroxides (LDHs) with adjustable metal ion composition and alterable interlayer structure possessing charming physicochemical characteristics, versatile bioactive properties, and excellent drug loading and delivery capabilities arise widespread attention and have achieved considerable achievements for bone disease treatment in the last decade. However, to the authors' best knowledge, no review has comprehensively summarized the advances of LDHs in treating bone disease so far. Herein, the advantages of LDHs for orthopedic disorders treatment are outlined and the corresponding state-of-the-art achievements are summarized for the first time. The potential of LDHs-based nanocomposites for extended therapeutics for bone diseases is highlighted and perspectives for LDHs-based scaffold design are proposed for facilitated clinical translation.

Bone tissue engineering for treating osteonecrosis of the femoral head.

Osteonecrosis of the femoral head (ONFH) is a devastating and complicated disease with an unclear etiology. Femoral head-preserving surgeries have been devoted to delaying and hindering the collapse of the femoral head since their introduction in the last century. However, the isolated femoral head-preserving surgeries cannot prevent the natural progression of ONFH, and the combination of autogenous or allogeneic bone grafting often leads to many undesired complications. To tackle this dilemma, bone tissue engineering has been widely developed to compensate for the deficiencies of these surgeries. During the last decades, great progress has been made in ingenious bone tissue engineering for ONFH treatment. Herein, we comprehensively summarize the state-of-the-art progress made in bone tissue engineering for ONFH treatment. The definition, classification, etiology, diagnosis, and current treatments of ONFH are first described. Then, the recent progress in the development of various bone-repairing biomaterials, including bioceramics, natural polymers, synthetic polymers, and metals, for treating ONFH is presented. Thereafter, regenerative therapies for ONFH treatment are also discussed. Finally, we give some personal insights on the current challenges of these therapeutic strategies in the clinic and the future development of bone tissue engineering for ONFH treatment.

Coupling Probiotics with 2D CoCuMo-LDH Nanosheets as a Tumor-Microenvironment-Responsive Platform for Precise NIR-II Photodynamic Therapy.

Photodynamic therapy (PDT) has become a promising cancer treatment approach with superior advantages. However, it remains a grand challenge to develop tumor microenvironment (TME)-responsive photosensitizers (PSs) for tumor-targeting precise PDT. Herein, the coupling Lactobacillus acidophilus (LA) probiotics with 2D CoCuMo layered-double-hydroxide (LDH) nanosheets (LA&LDH) is reported as a TME-responsive platform for precise NIR-II PDT. The CoCuMo-LDH nanosheets loaded on LA can be transformed from crystalline into amorphous through etching by the LA-metabolite-enabled low pH and overexpressed glutathione. The TME-induced in situ amorphization of CoCuMo-LDH nanosheets can boost its photodynamic activity for singlet oxygen (1 O2 ) generation under 1270 nm laser irradiation with relative 1 O2 quantum yield of 1.06, which is the highest among previously reported NIR-excited PSs. In vitro and in vivo assays prove that the LA&LDH can effectively achieve complete cell apoptosis and tumor eradication under 1270 nm laser irradiation. This study proves that the probiotics can be used as a tumor-targeting platform for highly efficient precise NIR-II PDT.

Boosting the Sonodynamic Cancer Therapy Performance of 2D Layered Double Hydroxide Nanosheet-Based Sonosensitizers Via Crystalline-to-Amorphous Phase Transformation.

Sonodynamic therapy (SDT) has been a promising therapeutic modality for cancer because of its superior advantages compared with other therapeutic strategies. However, the current sonosensitizers used for SDT normally exhibit low activity for ultrasound (US)-induced reactive oxygen species (ROS) generation. Herein, the crystalline-to-amorphous phase transformation is reported as a simple but powerful strategy to engineer ultrathin 2D CoW-LDH and NiW-LDH nanosheets as highly efficient sonosensitizers for SDT. The phase transformation of CoW-LDH and NiW-LDH nanosheets from polycrystalline to amorphous ones is achieved through a simple acid etching treatment. Importantly, compared with the polycrystalline one, the amorphous CoW-LDH (a-CoW-LDH) nanosheets possess higher ROS generation activity under US irradiation, which is ≈17 times of the commercial TiO2 sonosensitizer. The results suggest that the enhanced performance of ultrathin a-CoW-LDH nanosheets for US-induced ROS generation may be attributed to the phase transformation-induced defect generation and electronic structure changes. After polyethylene glycol modification, the a-CoW-LDH nanosheets can serve as a high-efficiency sonosensitizer for SDT to achieve cell death in vitro and tumor eradication in vivo under US irradiation.

Preparation of 2D Polyaniline/MoO3- x Superlattice Nanosheets via Intercalation-Induced Morphological Transformation for Efficient Chemodynamic Therapy.

Organic intercalation of layered nanomaterials is an attractive strategy to fabricate organic/inorganic superlattices for a wide range of promising applications. However, the synthesis of 2D organic/inorganic superlattice nanosheets remains a big challenge. Herein, the preparation of 2D polyaniline/MoO3- x (PANI/MoO3- x ) superlattice nanosheets via intercalation-induced morphological transformation from MoO3  nanobelts, as efficient Fenton-like reagents for chemodynamic therapy (CDT), is reported. Micrometer-long MoO3  nanobelts are co-intercalated with Na+ /H2 O followed by the guest exchange with aniline monomer for in situ polymerization to obtain PANI/MoO3- x nanosheets. Intriguingly, the PANI intercalation can induce the morphological transformation from long MoO3  nanobelts to 2D PANI/MoO3- x nanosheets along with the partial reduction of Mo6+ to Mo5+ , and generation of rich oxygen vacancies. More importantly, thanks to the PANI intercalation-induced activation, the PANI/MoO3- x nanosheets exhibit excellent Fenton-like catalytic activity for generation of hydroxyl radical (·OH) by decomposing H2 O2  compared with the MoO3  nanobelts. It is speculated that the good conductivity of PANI can facilitate electron transport during the Fenton-like reaction, thereby enhancing the efficiency of CDT. Thus, the polyvinylpyrrolidone-modified PANI/MoO3- x nanosheets can function as Fenton-like reagents for highly efficient CDT to kill cancer cells and eradicate tumors.

A MgFe-LDH Nanosheet-Incorporated Smart Thermo-Responsive Hydrogel with Controllable Growth Factor Releasing Capability for Bone Regeneration.

Although growth factor (GF)-loaded hydrogels have been explored as promising materials in repairing bone defects, it still remains challenging to construct smart hydrogels with excellent gelation/mechanical properties as well as controllable GF releasing capability. Herein, the incorporation of bone morphogenetic protein 2 (BMP-2)-functionalized MgFe-layered double hydroxide (LDH) nanosheets into chitosan/silk fibroin (CS) hydrogels loaded with platelet-derived growth factor-BB (PDGF-BB) to construct a smart injectable thermo-responsive hydrogel (denoted as CSP-LB), which can achieve a burst release of PDGF-BB and a sustained release of BMP-2, for highly efficient bone regeneration is reported. The incorporation of MgFe-LDH in CS hydrogel not only shortens the gelation time and decreases sol-gel transition temperature, but also enhances the mechanical property of the hydrogel. Because of the sequential release of dual-GFs and sustained release of bioactive Mg2+ /Fe3+ ions, the in vitro experiments prove that the CSP-LB hydrogel exhibits excellent angiogenic and osteogenic properties compared with the CS hydrogel. In vivo experiments further prove that the CSP-LB hydrogel can significantly enhance bone regeneration with higher bone volume and mineral density than that of the CS hydrogel. This smart thermo-sensitive CSP-LB hydrogel possesses excellent gelation capability and angiogenic and osteogenic properties, thus providing a promising minimally invasive solution for bone defect treatment.

Surface Functionalization of Hydroxyapatite Scaffolds with MgAlEu-LDH Nanosheets for High-Performance Bone Regeneration.

Although artificial bone repair scaffolds, such as titanium alloy, bioactive glass, and hydroxyapatite (HAp), have been widely used for treatment of large-size bone defects or serious bone destruction, they normally exhibit unsatisfied bone repair efficiency because of their weak osteogenic and angiogenesis performance as well as poor cell crawling and adhesion properties. Herein, the surface functionalization of MgAlEu-layered double hydroxide (MAE-LDH) nanosheets on porous HAp scaffolds is reported as a simple and effective strategy to prepare HAp/MAE-LDH scaffolds for enhanced bone regeneration. The surface functionalization of MAE-LDHs on the porous HAp scaffold can significantly improve its surface roughness, specific surface, and hydrophilicity, thus effectively boosting the cells adhesion and osteogenic differentiation. Importantly, the MAE-LDHs grown on HAp scaffolds enable the sustained release of Mg2+ and Eu3+ ions for efficient bone repair and vascular regeneration. In vitro experiments suggest that the HAp/MAE-LDH scaffold presents much enhanced osteogenesis and angiogenesis properties in comparison with the pristine HAp scaffold. In vivo assays further reveal that the new bone mass and mineral density of HAp/MAE-LDH scaffold increased by 3.18- and 2.21-fold, respectively, than that of pristine HAp scaffold. The transcriptome sequencing analysis reveals that the HAp/MAE-LDH scaffold can activate the Wnt/ß-catenin signaling pathway to promote the osteogenic and angiogenic abilities.

Layered double hydroxide-based nanomaterials for biomedical applications.

Against the backdrop of increased public health awareness, inorganic nanomaterials have been widely explored as promising nanoagents for various kinds of biomedical applications. Layered double hydroxides (LDHs), with versatile physicochemical advantages including excellent biocompatibility, pH-sensitive biodegradability, highly tunable chemical composition and structure, and ease of composite formation with other materials, have shown great promise in biomedical applications. In this review, we comprehensively summarize the recent advances in LDH-based nanomaterials for biomedical applications. Firstly, the material categories and advantages of LDH-based nanomaterials are discussed. The preparation and surface modification of LDH-based nanomaterials, including pristine LDHs, LDH-based nanocomposites and LDH-derived nanomaterials, are then described. Thereafter, we systematically describe the great potential of LDHs in biomedical applications including drug/gene delivery, bioimaging diagnosis, cancer therapy, biosensing, tissue engineering, and anti-bacteria. Finally, on the basis of the current state of the art, we conclude with insights on the remaining challenges and future prospects in this rapidly emerging field.

Defect engineering of layered double hydroxide nanosheets as inorganic photosensitizers for NIR-III photodynamic cancer therapy.

Although two-dimensional (2D) layered double hydroxides (LDHs) have been widely used as efficient nanoagents for biological diagnosis and treatment, they have been found to be inert as photosensitizers (PSs) for photodynamic therapy (PDT). Herein, we report the defect engineering of ultrathin 2D CoMo-LDH and NiMo-LDH nanosheets as highly active inorganic PSs for PDT in the third near-infrared (NIR-III) window. Hydrothermal-synthesized 2D CoMo-LDH and NiMo-LDH nanosheets are etched via a simple acid treatment to obtain defect-rich CoMo-LDH and NiMo-LDH nanosheets. Importantly, the defect-rich CoMo-LDH nanosheets exhibit much higher activity (~97 times) for generation of reactive oxygen species than that of the pristine CoMo-LDH nanosheets under a NIR-III 1567 nm laser irradiation. Therefore, after modification with polyethylene glycol, the defect-rich CoMo-LDH nanosheets can be used as an efficient inorganic PS for PDT to efficiently induce cancer cells apoptosis in vitro and eradicate tumors in vivo under 1567 nm laser irradiation.

Thermo-responsive nano-in-micro particles for MRI-guided chemotherapy.

In this work, we develop nano-in-micro thermo-responsive microspheres as theranostic systems for anti-cancer hyperthermia. Firstly, layered double hydroxide (LDH) nanoparticles were synthesized and subsequently loaded with the chemotherapeutic agents methotrexate (MTX) or 5-fluorouracil (5FU). The drug-loaded LDH particles were then co-encapsulated with superparamagnetic iron oxide nanoparticles (SPIONs) into poly(acrylamide-co-acrylonitrile) microparticles via spray drying. The SPIONs are able to act as MRI contrast agents, thus resulting in potential theranostic formulations. Concave microparticles were observed by electron microscopy, and elemental mapping results suggest the LDH and SPION particles were homogeneously distributed inside the microparticles. In vitro dissolution tests showed that the drug was released over a prolonged period of time with the microspheres having distinct release curves at 37 and 43 °C. The relaxivity (r2) profiles were also found to be different over the temperature range 35 to 46 °C. Mathematical relationships between r2, release and temperature data were established, demonstrating that the microparticles have the potential for use in MRI-guided therapy. In vitro cell experiments revealed that the formulations permit synergistic hyperthermia-aided chemotherapy in cultured Caco-2 and A549 cells. Thus, the microparticles prepared in this work have potential as smart stimuli-responsive theranostics for hyperthermia-aided chemotherapy.

Preparation of Dye Molecule-Intercalated MoO3 Organic/Inorganic Superlattice Nanoparticles for Fluorescence Imaging-Guided Catalytic Therapy.

Intercalation of organic molecules into the van der Waals gaps of layered materials allows for the preparation of organic/inorganic superlattices for varying promising applications. Herein, the preparation of a series of dye molecule/MoO3 organic/inorganic superlattice nanoparticles by aqueous intercalation of several dye molecules into layered MoO3 for fluorescence imaging-guided catalytic therapy is reported. The long MoO3 nanobelts are treated by ball milling and subsequent aqueous intercalation followed by a cation ion exchange to obtain the dye molecule-intercalated MoO3 organic/inorganic superlattices. Importantly, because of the activation induced by organic intercalation, the Nile blue (NB)-intercalated MoO3-x (NB-MoO3-x ) nanoparticles show excellent catalytic activity for the generation of reactive oxygen species, that is, hydroxyl radical (·OH) and superoxide anion (·O2- ), through catalyzing H2 O2 and O2 , respectively. Moreover, the intense fluorescence of the intercalated NB molecules endows NB-MoO3-x with the in vivo fluorescence imaging capability. Thus, the polyvinylpyrrolidone-modified NB-MoO3-x nanoparticles can be used for tumor-specific catalytic therapy to realize efficient cancer cell elimination in vitro and fluorescence imaging-guided tumor ablation in vivo.

A pH-responsive ultrathin Cu-based nanoplatform for specific photothermal and chemodynamic synergistic therapy.

Noninvasive tumor therapy requires a new generation of bionanomaterials towards sensitive response to the unique tumor microenvironment to achieve accurate and effective treatment. Herein, we have developed a tumor therapy nanoplatform by immobilizing natural glucose oxidase (GOD) onto Cu-based layered double hydroxide (CuFe-LDH) nanosheets, which for the first time integrates acid-enhanced photothermal therapy (PTT), and pH-responsive and heat-facilitated chemodynamic therapy (CDT) simultaneously. As demonstrated by EXAFS and HRTEM, CuFe-LDH nanosheets possess a considerable number of defects caused by different acid conditions, resulting in a significantly acid-enhanced photothermal conversion efficiency (83.2% at pH 5.4 vs. 46.0% at pH 7.4). Moreover, GOD/CuFe-LDH nanosheets can convert a cascade of glucose into hydroxyl radicals (˙OH) under tumor acid conditions, which is validated by a high maximum velocity (V max = 2.00 × 10-7 M) and low Michaelis-Menten constant (K M = 12.01 mM). With the combination of PTT and CDT, the tumor tissue in vivo is almost eliminated with low-dose drug injection (1 mg kg-1). Therefore, this novel pH-responsive Cu-based nanoplatform holds great promise in tumor-specific CDT/PTT synergistic therapy.

Layered Double Hydroxide Modified Bone Cement Promoting Osseointegration via Multiple Osteogenic Signal Pathways.

Poly(methyl methacrylate) (PMMA) bone cement has been widely used in orthopedic surgeries including total hip/knee replacement, vertebral compression fracture treatment, and bone defect filling. However, aseptic loosening of the interface between PMMA bone cement and bone often leads to failure. Hence, the development of modified PMMA that facilitates the growth of bone into the modified PMMA bone cement is key to reducing the incidence of aseptic loosening. In this study, MgAl-layered double hydroxide (LDH) microsheets modified PMMA (PMMA&LDH) bone cement with superior osseointegration performance has been synthesized. The maximum polymerization reaction temperature of PMMA&LDH decreased by 7.0 and 11.8 °C, respectively, compared with that of PMMA and PMMA&COL-I (mineralized collagen I modified PMMA). The mechanical performance of PMMA&LDH decreased slightly in comparison with PMMA, which is beneficial to alleviate stress-shielding osteolysis, and indirectly promote osseointegration. The superior osteogenic ability of PMMA&LDH has been demonstrated in vivo, which boosts bone growth by 2.17- and 18.34-fold increments compared to the PMMA&COL-I and PMMA groups at 2 months, postoperatively. Moreover, transcriptome sequencing revealed four key osteogenic pathways: p38 MAPK, ERK/MAPK, FGF, and TGF-ß, which were further confirmed by IPA, qPCR, and Western blot assays. Hence, LDH-modified PMMA bone cement is a promising biomaterial to enhance bone growth with potential applications in relevant orthopedic surgeries.

Ultrathin chalcogenide nanosheets for photoacoustic imaging-guided synergistic photothermal/gas therapy.

Previous preclinical and clinical studies have shown that using only a single therapy makes it difficult to completely eradicate tumors and restrain cancer metastasis. To overcome this challenge, multi-modal synergistic treatments have attracted considerable attention. Herein, an ultrathin Cu-loaded CoCuFe-selenide (CCFS) was prepared by a facile topotactic transformation from CoCuFe layered double hydroxide (LDH) nanosheets (NSs), followed by surface modification with polyvinyl pyrrolidone (PVP) and l-arginine (L-Arg). The resultant CCFS-PVP-L-Arg (CPA) system shows excellent synergetic photothermal and gas therapy (PTT/GT). The CCFS NSs have strong LSPR absorbance characteristic, with enhanced light absorption in the near-infrared (NIR) region. This endows the CPA nanocomposite with an outstanding photothermal conversion efficiency of 72.0% (pH 7.4) and 81.0% (pH 5.4), among the highest reported for 2D chalcogenide nanomaterials. In addition, NO release from CPA is triggered by decomposition of L-Arg in the H2O2-rich and acidic tumor microenvironment, permitting localized NO gas therapy in the tumor site. In vitro experiments revealed 91.8% apoptosis of HepG2 cells, and in vivo studies showed complete tumor elimination upon treatment with the CPA nanocomposite under NIR irradiation. To the best of our knowledge, this is the first report of combined defect-induced high-efficiency PTT with H2O2 and pH targeted GT.

Recent advances in innovative strategies for enhanced cancer photodynamic therapy.

Photodynamic therapy (PDT), a non-invasive therapeutic modality, has received increasing attention owing to its high selectivity and limited side effects. Although significant clinical research progress has been made in PDT, the breadth and depth of its clinical application have not been fully realized due to the limitations such as inadequate light penetration depth, non-targeting photosensitizers (PSs), and tumor hypoxia. Consequently, numerous investigations put their emphasis on innovative strategies to overcome the aforementioned limitations and enhance the therapeutic effect of PDT. Herein, up-to-date advances in these innovative methods for PDT are summarized by introducing the design of PS systems, their working mechanisms and application examples. In addition, current challenges of these innovative strategies for clinical application, and future perspectives on further improvement of PDT are also discussed.