GAPDH-Silence Microsphere via Reprogramming Macrophage Metabolism and eradicating Bacteria for Diabetic infection bone regeneration.

Macrophage metabolism dysregulation, which is exacerbated by persistent stimulation in infectious and inflammatory diseases, such as diabetic infectious bone defects (DIBD), eventually leads to the failure of bone repair. Here, we have developed an injectable, macrophage-modulated GAPDH-Silence drug delivery system. This microsphere comprises chondroitin sulfate methacrylate (CM) and methacrylated gelatin (GM), while the dimethyl fumarate (DMF)-loaded liposome (D-lip) is encapsulated within the microsphere (CM@GM), named D-lip/CM@GM. Triggered by the over-expressed collagenase in DIBD, the microspheres degrade and release the encapsulated D-lip. D-lip could modulate metabolism by inhibiting GAPDH, which suppresses the over-activation of glycolysis, thus preventing the inflammatory response of macrophages in vitro. While beneficial for macrophages, D-lip/CM@GM is harmful to bacteria. GAPDH, while crucial for glycolysis of staphylococcal species (S. aureus), can be effectively countered by D-lip/CM@GM. We are utilizing existing drugs in innovative ways to target central metabolism for effective eradication of bacteria. In the DIBD model, our results confirmed that the D-lip/CM@GM enhanced bacteria clearance and reprogrammed dysregulated metabolism, thereby significantly improving bone regeneration. In conclusion, this GAPDH-Silence microsphere system may provide a viable strategy to promote diabetic infection bone regeneration.

Enhanced Therapeutic Potential of Hybrid Exosomes Loaded with Paclitaxel for Cancer Therapy.

The advancement of exosome studies has positioned engineered exosomes as crucial biomaterials for the development of advanced drug delivery systems. This study focuses on developing a hybrid exosome system by fusing mesenchymal stem cells (MSCs) exosomes with folate-targeted liposomes. The aim was to improve the drug loading capacity and target modification of exosome nanocarriers for delivering the first-line chemotherapy drug paclitaxel (PTX) and its effectiveness was assessed through cellular uptake studies to evaluate its ability to deliver drugs to tumor cells in vitro. Additionally, in vivo experiments were conducted using a CT26 tumor-bearing mouse model to assess the therapeutic efficacy of hybrid exosomes loaded with PTX (ELP). Cellular uptake studies demonstrated that ELP exhibited superior drug delivery capabilities to tumor cells in vitro. Moreover, in vivo experiments revealed that ELP significantly suppressed tumor growth in the CT26 tumor-bearing mouse model. Notably, for the first time, we examined the tumor microenvironment following intratumoral administration of ELP. We observed that ELP treatment activated CD4+ and CD8+ T cells, reduced the expression of M2 type tumor-associated macrophages (TAMs), polarized TAMs towards the M1 type, and decreased regulatory T cells (Tregs). Our research highlights the considerable therapeutic efficacy of ELP and its promising potential for future application in cancer therapy. The development of hybrid exosomes presents an innovative approach to enhance drug delivery and modulate the tumor microenvironment, offering exciting prospects for effective cancer treatment strategies.

Association between C-Reactive protein and periodontitis in an obese population from the NHANES 2009-2010.

BACKGROUND: Various data have been obtained on the relationship between body mass index (BMI) and C-reactive protein (CRP) and periodontitis. The aim of this study was to determine whether CRP/BMI are associated with periodontitis using data from the National Health and Nutrition Examination Survey (NHANES) database. METHODS: A cross-sectional analysis of data from 3602 participants in the 2009-2010 NHANES cycle was performed. The definition of periodontitis was used to divide participants into four groups according to the criteria of Eke. Correlations between CRP/BMI and periodontitis were tested for statistical significance by means of descriptive statistics, multivariate regression, and subgroup-stratified analyses, with and without adjustments for confounders (such as age and sex). RESULTS: There were no statistically significant differences (p > 0.05) regarding BMI and the development of periodontitis. After adjustment for age, sex, race, marital status, annual family income, alcohol consumption, hypertension, smoking, chronic pulmonary disease, cardiovascular disease, diabetes, flossing, and arthritis, CRP correlated significantly with the development of periodontitis in the subgroups stratified by obesity, with an odds ratio (OR) of 1.2 (95% CI, 1.0 to 1.5). CONCLUSION: Through data analysis, we found an association between CRP levels and periodontitis prevalence in the American population, although this association was only present in the obese population. While there are several hypotheses about the underlying mechanism, further studies are needed to validate these findings.

A simple strategy for the detection of Pb(II) and Cu(II) by an electrochemical sensor based on Zn/Ni-ZIF-8/XC-72/Nafion hybrid materials.

In this study, a novel electrochemical sensor for simultaneous detection of Pb(II) and Cu(II) was constructed by using Zn/Ni-ZIF-8/XC-72/Nafion hybrid material as electrode surface modifier. XRD, FT-IR, XPS and SEM were used to study the crystal structure, functional groups, element types and morphologies of the prepared materials. The electrochemical performance of the Zn/Ni-ZIF-8/XC-72/Nafion/GCE sensor were investigated by CV, EIS and DPV. In addition, the effects of various conditions including pH, the type of buffer and the ratio of Zn/Ni-ZIF-8 to XC-72 were also explored for the determination of Pb(II) and Cu(II). Under the optimum conditions, the constructed sensor exhibited outstanding linear response of Pb(II) (0.794-39.6 ppm) and Cu(II) (0.397-19.9 ppm) with detection limits of 0.0150 and 0.0096 ppm, respectively. Finally, the fabricated sensor was further used to detect Pb(II) and Cu(II) in real samples, and the satisfactory recovery was obtained.

Scar Tissue-Targeting Polymer Micelle for Spinal Cord Injury Treatment.

Spinal cord injury (SCI) is a devastating disorder, leading to permanent motor and sensory deficit. Despite recent advances in neurosciences, the treatment efficacy on SCI patients remains unsatisfactory, mainly due to the poor accumulation, short retention, and lack of controlled release of therapeutics in lesion tissue. Herein, an injured spinal cord targeting prodrug polymer micelle is built. An esterase-responsive bond is used to link apocynin (APO) monomer, because of the enhanced esterase activity found in microglia cells after activation, which ensures a controlled degradation of APO prodrug (Allyloxypolyethyleneglycol-b-poly [2-(((4-acetyl-2-methoxyphenoxy)carbonyl)oxy)ethyl methacrylate], APEG-PAPO or PAPO) by activated microglia cells. A scar tissue-homing peptide (cysteine-alanine-glutamine-lysine, CAQK) is introduced to the PAPO to endow the polymer micelle the lesion tissue-targeting ability. As a result, this CAQK-modified prodrug micelle (cPAM) exhibits an improved accumulation and prolonged retention in lesion tissue compared to the control micelle. The cPAM also leads to superior tissue protection and sustained motor function recovery than the control groups in a mouse model of SCI. In conclusion, the cPAM induces an effective treatment of SCI by the lesion tissue specific delivery of the prodrug polymer via its robust scar binding effect, making the scar tissue a drug releasing platform for sustained treatment of SCI.

Facile Hydrophobization of siRNA with Anticancer Drug for Non-Cationic Nanocarrier-Mediated Systemic Delivery.

The inherent features of small interfering RNA (siRNA), including a relatively high molecular weight, negative charge, and hydrophilic nature, lead to the widespread use of cationic polymers and lipid-based nanocarriers, which might induce potential cytotoxicity, thus limiting their clinical application. Here, we report a facile strategy for changing the inherent features of siRNA molecules by achieving hydrophobization. We found that the simple mixing of siRNA and doxorubicin hydrochloride (DOX·HCl) could form a hydrophobic complex, which was readily encapsulated into noncationic PEG- b-PLA micelles for systemic delivery. In addition to delivering DOX·HCl, this strategy could be extended to deliver other hydrochloride forms of anticancer drugs with large hydrophobic domains. This facile strategy efficiently avoids the use of cationic nanocarriers, providing a new avenue for siRNA delivery.

Direct Nucleus-Targeted Drug Delivery Using Cascade pHe /Photo Dual-Sensitive Polymeric Nanocarrier for Cancer Therapy.

The cell nucleus-targeted delivery of therapeutic agents plays a critical role in cancer therapy, since the biological target of many anticancer therapeutics is the cell nucleus. However, multiple physiological barriers limit the delivery efficiency of free drugs, resulting in unsatisfactory therapeutic effects. Herein, thioketal crosslinked polyphosphoester-based nanoparticles with a tumor acidity (pHe )-sensitive transactivator of transcription (TAT) peptide (DA-masked TAT-decorating reactive oxygen species (ROS)-sensitive Ce6/DOX-loaded hyperbranched nanoparticles (D TRCD)) are explored for cascade nucleus-targeted drug delivery. Following administration, D TRCD experiences prolonged circulation by masking the targeting effect of its TAT peptide and then achieves enhanced tumor cell uptake and improved translocation into the perinuclear region by reactivating the TAT targeting capability in tumor tissue. Subsequently, ROS generated by D TRCD under 660 nm laser not only disrupts the nuclear membrane to allow entry into the nuclei but also triggers intracellular release of the payload in the nuclei. As evidenced by in vivo experiments, such pHe /photo dual-sensitive polymeric nanocarriers offer remarkable therapeutic effects, efficiently suppressing tumor growth. This multistage cascade nucleus-targeted drug delivery concept provides new avenues to develop nucleus-targeted drug delivery systems.

Synthesis of an Oxidation-Sensitive Polyphosphoester Bearing Thioether Group for Triggered Drug Release.

In this work, novel amphiphilic diblock copolymers of polyethylene glycol and polyphosphoester with pendant thioether groups, denoted as mPEG- b-PMSPEP, were synthesized through the ring-opening polymerization of functionalized cyclic phosphoester monomer using methoxy poly(ethylene glycol) and Sn(Oct)2 as the macroinitiator and catalyst, respectively. The successful synthesis was confirmed by 1H, 13C, 31P nuclear magnetic resonance (NMR) and gel permeation chromatography (GPC). These amphiphilic block copolymers self-assembled spontaneously in the aqueous solution, and the formed nanoparticles were sensitive to the oxidation that induced the hydrophobic to hydrophilic transition for its PMSPEP core under triggering of H2O2 and the subsequent dissociation of the nanoparticles. In addition, the reactive oxygen species (ROS) generated by light and the photosensitizer were also capable of carrying out the oxidation of these nanoparticles. Their oxidation profiles were systemically evaluated by 1H NMR. Finally, the mPEG- b-PMSPEP nanoparticles were used to coencapsulate the photosensitizer chlorin e6 (Ce6) and anticancer drug paclitaxel (PTX), achieving the photoaccelerated PTX release via oxidation of the nanoparticles by the generated ROS under light irradiation. Meanwhile, the in vitro cytotoxicity assays indicated that these nanoparticles coencapsulated with PTX and Ce6 showed a combined cell-killing effect toward MDA-MB-231 tumor cells, exhibiting great potential for drug delivery systems that realize the synergistic chemo-photodynamic therapy for cancer treatment.

Embolization of brain arteriovenous malformations with the diluted Onyx technique: initial experience.

PURPOSE: Insufficient nidus occlusion is a matter of great concern to routine Onyx embolization of brain arteriovenous malformations (AVMs). This paper described an efficient method which using the diluted Onyx embolization technique to treat brain AVM. METHODS: The diluted Onyx technique was performed in a series of 15 patients with brain AVMs (10 males, 5 females; age range, 11-44 years). It consists of initial embolization with routine Onyx-18, followed by the diluted Onyx (1.5 mL of Onyx-18 diluted with 0.5 mL of DMSO) through the same microcatheter. The technical skills and angiographic and clinical outcomes were analyzed. RESULTS: A total of 15 embolization sessions were performed with diluted Onyx via 16 arterial feeders in these 15 patients. Each patient underwent one attempt of diluted Onyx through a single feeder except one patient. In this patient, the AVM was simultaneously embolized with diluted Onyx through double microcatheters which were placed in two feeders. When the length of reflux reached to 2 cm (or close to the determined length) and the embolic material could not move distally any more despite some rounds of "injection-reflux-waiting," regular Onyx 18 was changed to diluted Onyx. Antegrade flow of embolic material into the nidus was observed in 12 cases but failed in 3. An average of 90% (range 55-100%) estimated size reduction was achieved, and 6 AVMs were completely obliterated. No functionally relevant complications occurred. CONCLUSION: The diluted Onyx technique could be a useful adjunct to routine Onyx embolization which may offer more embolic material penetrating into the nidus of AVM, but additional work is needed to validate this technique.

Effects of nano-TiO2 -LDPE packaging on postharvest quality and antioxidant capacity of strawberry (Fragaria ananassa Duch.) stored at refrigeration temperature.

BACKGROUND: Nano-TiO2 -low-density polyethylene (NTLDPE) packaging was prepared, and the effects of NTLDPE packaging on quality and antioxidant capacity of strawberry fruits were investigated. RESULTS: With increased barrier properties, NTLDPE packaging quickly formed a relative lower O2 and higher CO2 air composition in comparison with LDPE. It was also more efficient in maintaining the overall quality of strawberry fruit, as reflected by lower decay rate and weight loss, as well as retarding the decrease in firmness and titratable acid. Meanwhile, reactive oxygen species (ROS) including superoxide anion and hydrogen peroxide in NTLDPE-packed fruits were 10.8% and 21.9% lower, respectively. Furthermore, the activities of antioxidant enzymes involved in ROS scavenging in NTLDPE-packed fruits were significantly higher at the later period of storage time. Anthocyanin accumulation was inhibited, whereas ascorbic acid and total phenolics contents were better retained and 1-diphenyl-2-picrylhydrazyl radical scavenging activity was 13.2% higher in NTLDPE-packed fruit by the end of storage. CONCLUSION: These data indicate that the beneficial effects of NTLDPE packaging on postharvest quality and antioxidant capacity of strawberry are probably associated with the promotion of ROS scavenging and related antioxidant enzyme activities, and NTLDPE packaging together with refrigeration storage is a promising method for strawberry fruit preservation. © 2016 Society of Chemical Industry.

Preparation of Puerarin Long Circulating Liposomes and its Effect on Osteoporosis in Castrated Rats.

Osteoporosis is a disease that causes low bone mass and deterioration of bone microarchitecture. Puerarin is a natural isoflavone compound that has been shown to possess anti-inflammatory, antioxidant and ameliorative effects on osteoporosis with less adverse reactions. However, its fast metabolism and low oral bioavailability limit its application. This study aimed to prepare d-α-tocopherol polyethylene glycol 1000 succinate (TPGS)- modified Puerarin Long Circulating Liposomes (TPGS-Puerarin-liposomes), in order to improve the oral bioavailability of puerarin, before evaluation of its pharmacological activity in vitro and in vivo. We employed film dispersion method to develop TPGS-Puerarin-liposomes before appropriate characterizations. Afterwards, we utilized in vivo imaging, pharmacokinetic analysis and in vitro drug release testing to further evaluate the in vivo and in vitro delivery efficiency. In addition, we established a castrated osteoporosis rat model to observe the changes in femur tissue structure and bone micromorphology via hematoxylin-eosin (HE) staining and Micro Computed Tomography (Micro CT). Besides, levels of oxidative stress and inflammatory indicators, as well as expression of wnt/ß-catenin pathway-related proteins were detected. In terms of physiochemical properties, the respective mean particle size (PS) and zeta potential (ZP) of TPGS-Puerarin-liposomes were 76.63±0.59 nm and -25.54±0.11 mV. The liposomal formulation exhibited encapsulation efficiency (EE) of 95.08±0.25% and drug loading (DL) of 7.84±0.07%, along with excellent storage stability. Compared with free drugs, the TPGS-Puerarin-liposomes demonstrated a sustained release effect and could increase blood concentration of puerarin in rats, thereby significantly improving its bioavailability. Also, in vivo studies have confirmed potential of the liposomes to promote bone tissue targeting and accumulation of puerarin, coupled with significant improvement of the osteoporotic status. Besides, the liposomes could also reduce levels of oxidative stress and inflammatory factors in serum and bone tissue. Additionally, we discovered that TPGS-Puerarin-liposomes increased Wnt, ß-catenin and T-cell factor (TCF) expressions at protein level in the wnt/ß-catenin signaling pathway. This study has demonstrated the potential of TPGS-Puerarin-liposomes for treatment of osteoporosis.

Heterologous Prime-Boost Immunization Strategies Using Varicella-Zoster Virus gE mRNA Vaccine and Adjuvanted Protein Subunit Vaccine Triggered Superior Cell Immune Response in Middle-Aged Mice.

Purpose: Heterologous immunization using different vaccine platforms has been demonstrated as an efficient strategy to enhance antigen-specific immune responses. In this study, we performed a head-to-head comparison of both humoral and cellular immune response induced by different prime-boost immunization regimens of mRNA vaccine and adjuvanted protein subunit vaccine against varicella-zoster virus (VZV) in middle-aged mice, aiming to get a better understanding of the influence of vaccination schedule on immune response. Methods: VZV glycoprotein (gE) mRNA was synthesized and encapsulated into SM-102-based lipid nanoparticles (LNPs). VZV-primed middle-aged C57BL/6 mice were then subjected to homologous and heterologous prime-boost immunization strategies using VZV gE mRNA vaccine (RNA-gE) and protein subunit vaccine (PS-gE). The antigen-specific antibodies were evaluated using enzyme-linked immunosorbent assay (ELISA) analysis. Additionally, cell-mediated immunity (CMI) was detected using ELISPOT assay and flow cytometry. Besides, in vivo safety profiles were also evaluated and compared. Results: The mRNA-loaded lipid nanoparticles had a hydrodynamic diameter of approximately 130 nm and a polydispersity index of 0.156. Total IgG antibody levels exhibited no significant differences among different immunization strategies. However, mice received 2×RNA-gE or RNA-gE>PS-gE showed a lower IgG1/IgG2c ratio than those received 2×PS-gE and PS-gE> RNA-gE. The CMI response induced by 2×RNA-gE or RNA-gE>PS-gE was significantly stronger than that induced by 2×PS-gE and PS-gE> RNA-gE. The safety evaluation indicated that both mRNA vaccine and protein vaccine induced a transient body weight loss in mice. Furthermore, the protein vaccine produced a notable inflammatory response at the injection sites, while the mRNA vaccine showed no observable inflammation. Conclusion: The heterologous prime-boost strategy has demonstrated that an mRNA-primed immunization regimen can induce a better cell-mediated immune response than a protein subunit-primed regimen in middle-aged mice. These findings provide valuable insights into the design and optimization of VZV vaccines with the potentials to broaden varicella vaccination strategies in the future.

Effects of microplastic combined with Cr(III) on apoptosis and energy pathway of coral endosymbiont.

The combined effect of polyethylene (PE) microplastics and chromium (Cr(III)) on the scleractinian coral Acropora pruinosa (A. pruinosa) was investigated. The endpoints analysed in this study included the endosymbiont density, the chlorophyll a + c content, and the activity of enzymes involved in apoptosis (caspase-1, caspase-3), glycolysis (lactate dehydrogenase, LDH), the pentose phosphate pathway (glucose-6-phosphate dehydrogenase, G6PDH) and electron transfer coenzyme (nicotinamide adenine dinucleotide, NAD+/NADH). During the 7-day exposure to PE and Cr(III) stress, the endosymbiont density and chlorophyll content decreased gradually. The caspase-1 and caspase-3 activities increased in the high-concentration Cr(III) exposure group. Furthermore, the LDH and G6PDH activities decreased significantly, and the NAD+/NADH was decreased significantly. In summary, the results showed that PE and Cr(III) stress inhibited the endosymbiont energy metabolism enzymes and further led to endosymbiont apoptosis in coral. In addition, under exposure to the combination of stressors, when the concentration of Cr(III) remained at 1 × 10-2 mg/L, the toxic effects of heavy metals on the endosymbiont were temporarily relieved with elevated PE concentrations. In contrast, when coral polyps were exposed to 5 mg/L PE and increasing Cr(III) concentrations, their metabolic activities were seriously disturbed, which increased the burden of energy consumption. In the short term, the toxic effect of Cr(III) was more obvious than that of PE because Cr(III) exposure leads to endosymbiont apoptosis and irreversible damage. This is the first study to provide insights into the combined effect of microplastic and Cr(III) stress on the apoptosis and energy pathways of coral endosymbionts. This study suggested that microplastics combined with Cr(III) are an important factor affecting the apoptosis and energy metabolism of endosymbionts, accelerating the collapse of the balance between the coral host and symbiotic endosymbiont.

Interlocking-interface-enabled thermally deformable liquid metal/polymer membrane with high bonding strength.

HYPOTHESIS: The high surface tension of liquid metal (LM) causes interface incompatibility and poor bonding strength with many substrates. Fine adjustment towards the properties of the surface area is sufficient to introduce strong bonding. Hence, we hypothesize that the interlocking structure using hydrophilic polyvinyl alcohol (PVA) as a "bridge" should be helpful for tight interfacial bonding of LM with polymeric substrates, thus achieving high-performance LM/polymer membranes, which have wide applications in the field of soft sensors and robotics. EXPERIMENTS: The bulk EGaIn was fabricated into LM nanoparticles (LMNPs@PVA) solution. Then, PVA molecules were "doped" into the surface crosslink of the plasma treated polymer substrate by an interfacial penetrating method. Afterward, the solution was evenly dropped on the surface of the treated substrate to obtain the LMNP/polymer membrane after the water evaporated. Photothermal actuators were fabricated based on the membranes. FINDINGS: During the interlocking structure, PVA macromolecules could be doped and trapped onto the top surfaces of various polymer substrates as binding "bridges" between the LMNPs and the matrix materials. The achieved LMNP membrane exhibites satisfactory bonding strength, durability and water-assisted erase-reprint, which can be used as soft photothermal actuators with remote laser control.

Combined effects of copper and microplastics on physiological parameters of Tubastrea aurea corals.

Microplastics (MPs) have been a serious environmental problem because it can carry pollution like heavy metals and organic pollutants. However, the combined effect of MPs and bivalent copper ion (Cu(II)) on the coral azooxanthellate has been rarely studied. In the present study, the combined effects of PVC and Cu(II) on the physiological responses of Tubastrea aurea were studied. Our results showed that MPs alone enhanced the activity of catalase (CAT), superoxide dismutase (SOD), and reduced glutathione (GSH). The mixture groups had the same effects on the CAT and GSH, which enhanced CAT and GSH activity by 97% and 53% respectively. MPs alone and the combined treatment groups decreased the activity of lipid peroxide (LPO) and the content of metallothionein (MT) by 45% and 20% of the coral Tubastrea aurea. Cu(II) exposure always had negative effect on the physiological parameters of coral, and MPs decreased the toxicity of Cu(II) in the combined groups. This work is the first time to report the combined effects of Cu(II) and microplastics on azooxanthellate coral, which will provide important preliminary data for the following research.

GMT8 aptamer conjugated PEGylated Ag@Au core-shell nanoparticles as a novel radiosensitizer for targeted radiotherapy of glioma.

Radiotherapy is one of the main treatment modalities for glioma, but the therapeutic efficacy is often limited by the radioresistance of tumor cells. The radiosensitization effects of silver nanoparticles (AgNPs) and gold nanoparticles (AuNPs) on tumors have been confirmed by previous studies. To enhance the specific killing effect of irradiation on tumor cells, targeted modification of radiosensitizers is urgently needed. Herein, we developed polyethylene glycol (PEG)-coated Ag@Au core-shell nanoparticles (PSGNPs) modified with GMT8 aptamer (GSGNPs) and evaluated their radiosensitization effects on glioma cells through in vivo and in vitro experiments. Transmission electron microscope image showed that the prepared PSGNPs had a spherical core-shell structure with an average size of 11 nm. The ultraviolet-visible absorption spectra and Fourier transform infrared spectra displayed that GMT8 was successfully conjugated to PSGNPs. The results of dark-field imaging revealed that the targeting ability of GSGNPs to U87 glioma cells was much better than that to normal human microvascular endothelial cells. Additionally, it was also found that the endocytic pathways of GSGNPs mainly involved clathrin-mediated endocytosis and macropinocytosis. The sensitization enhancement ratio of GSGNPs was calculated to be 1.62, which was higher than that of PSGNPs. In vivo imaging results showed that GSGNPs exhibited good tumor targeting and retention capabilities, and the fluorescence intensity ratio of Cy5-GSGNPs to Cy5-PSGNPs reached a peak at 4 h after injection. More importantly, the median survival time of mice bearing U87 glioma was significantly prolonged after intravenous administration of GSGNPs combined with radiotherapy. This work demonstrated that GSGNPs could be used as an effective nano-radiosensitizer for targeted radiotherapy of glioma.

The effect of AS1411 surface density on the tumor targeting properties of PEGylated silver nanotriangles.

Aim: To determine the optimal AS1411 density on polyethylene glycol (PEG)ylated silver nanotriangles (PNTs) for targeting breast cancer cells. Methods: PNTs modified with different AS1411 densities (ANTs) were constructed, characterized and evaluated for their targeting properties in breast cancer cells and a mouse model of breast cancer. Results: AS1411 was successfully conjugated to PNTs. The accumulation and cellular uptake of 10-ANTs were the highest. 10-ANTs plus near-IR laser irradiation displayed the greatest inhibitory effect on cell viability. However, 5-ANTs had the highest accumulation in tumor tissues. When combined with NIR laser, 5-ANTs exhibited the best in vivo photothermal therapy effect. Conclusion: The optimal AS1411 densities at the cellular and animal levels were 10% and 5%, respectively.

Strength enhancement and modulus modulation in auxetic meta-biomaterials produced by selective laser melting.

Meta-biomaterials are applied to orthopedic implants to avoid stress shielding effects; however, there is no reason for the yield strength to be comparable to that of human bone. In this study, a composite unit cell was designed by combining the positive Poisson's ratio (PPR) and negative Poisson's ratio (NPR) unit cells, inspired by the second-phase strengthening theory. The purpose was to increase the strength while maintaining the elastic modulus. All structures were successfully fabricated from Ti-6Al-4V via selective laser melting. The relative density is between 0.08 and 0.24, which falls within the optimal range for bone growth. Mechanical tests indicated that the center of the inclined rod fractured in a stepwise fracture mode, which was consistent with the predictions of the Johnson-Cook model. The elastic modulus ranged from 0.652 ± 0.016 to 5.172 ± 0.021 GPa, and the yield strength varied from 10.62 ± 0.112 to 87.158 ± 2.215 MPa. An improved Gibson-Ashby law was proposed to facilitate the design of gradient structures. When the re-entrant angle was 40°, a hybrid body-centered cubic NPR structure was formed, resulting in a significant improvement in the mechanical properties. Importantly, the yield strength of the proposed composite structures increased by 43.23%, and the compression strength increased by 44.70% under the same elastic modulus. The strengthening mechanism has been proven to apply to other bending-dominated structures. Overall, this imparts unprecedented mechanical performance to auxetic meta-biomaterials and provides insights into improving the reported porous structures. STATEMENT OF SIGNIFICANCE: Auxetic meta-biomaterials exhibit auxetic properties that can improve the contact between the bone-implant interface and reduce the risk of aseptic failure. To avoid the stress shielding effect, the elastic modulus has traditionally been decreased by increasing the porosity. However, the strength is simultaneously reduced. Therefore, a composite unit cell was proposed to increase strength rather than modulus by combining the positive and negative Poisson's ratio unit cells, inspired by the second-phase strengthening theory. We observed a 43.23% increase in the yield strength of the composite structure without increasing the elastic modulus. This strengthening mechanism has been proven to apply to other bending-dominated structures. Our approach provides insights into improving other bending-dominated structures and broadening their applications for bone implantation.

Self-assembling ferrimagnetic fluorescent micelles for bioimaging guided efficient magnetic hyperthermia therapy.

Multifunctional magnet-fluorescent nanocomposites are widely applied in biomedical applications. Incorporating biocompatible quantum dots with highly ferrimagnetic magnetic nanoparticles into one nanoplatform for achieving efficient magnetic hyperthermia therapy (MHT) is very important. Herein, we reported an amphiphilic block copolymer with a flowable hydrophobic chain to encapsulate highly ferrimagnetic magnetic nanoparticles and ZnS/InP quantum dots via a facile self-assembly method. The obtained ferrimagnetic fluorescent micelle (FMFM) exhibited a uniform diameter of about 180 nm. In stark contrast, larger aggregation (400 nm in diameter) inevitably occurred using common poly(D,L-lactide) (PLA)-based amphiphilic block copolymer with a rigid hydrophobic chain, which was readily cleared by the reticuloendothelial system (RES). The flowable FMFM exhibited long-term colloidal stability within one month and desired fluorescent stability within 84 h. Benefiting from the high ferrimagnetism, the FMFM revealed excellent magnetic heating effect and magnetic resonance imaging capability. With accurate manipulation under an external magnetic field, FMFM realized in vitro enhanced fluorescence imaging sensitivity and accumulation efficiency at the tumor region, achieving in vitro and vivo improved MHT efficacy.

Cell-Derived Extracellular Matrix Materials for Tissue Engineering.

The involvement of cell-derived extracellular matrix (CDM) in assembling tissue engineering scaffolds has yielded significant results. CDM possesses excellent characteristics, such as ideal cellular microenvironment mimicry and good biocompatibility, which make it a popular research direction in the field of bionanomaterials. CDM has significant advantages as an expansion culture substrate for stem cells, including stabilization of phenotype, reversal of senescence, and guidance of specific differentiation. In addition, the applications of CDM-assembled tissue engineering scaffolds for disease simulation and tissue organ repair are comprehensively summarized; the focus is mainly on bone and cartilage repair, skin defect or wound healing, engineered blood vessels, peripheral nerves, and periodontal tissue repair. We consider CDM as a highly promising bionic biomaterial for tissue engineering applications and propose a vision for its comprehensive development. Impact statement Cell-derived extracellular matrix (CDM) has received continued attention on the field of tissue engineering because of its promising biological characteristics. CDM deposited in vitro is rich in protein fractions and contains a wealth of biological information that provides a suitable niche for the survival and activity of isolated cells. More importantly, the free-assembling feature of CDM allows it to participate in the assembly of tissue-engineered scaffolds, imparting bionic properties to regenerative scaffolds, and thus CDM-modified scaffolds are widely used in the reconstruction of bone and cartilage tissue, peripheral nerves, skin, and blood vessels. This article is dedicated to summarizing the important results achieved by CDM-modified tissue engineering scaffolds in tissue organ reconstruction, helping readers to understand the developments in this field in recent years.