Mitochondria-Regulated Information Processing Nanosystem Promoting Immune Cell Communication for Liver Fibrosis Regression.

Liver fibrosis is a coordinated response to tissue injury that is mediated by immune cell interactions. A mitochondria-regulated information-processing (MIP) nanosystem that promotes immune cell communication and interactions to inhibit liver fibrosis is designed. The MIP nanosystem mimics the alkaline amino acid domain of mitochondrial precursor proteins, providing precise targeting of the mitochondria. The MIP nanosystem is driven by light to modulate the mitochondria of hepatic stellate cells, resulting in the release of mitochondrial DNA into the fibrotic microenvironment, as detected by macrophages. By activating the STING signaling pathway, the developed nanosystem-induced macrophage phenotype switches to a reparative subtype (Ly6Clow) and downstream immunostimulatory transcriptional activity, fully restoring the fibrotic liver to its normal tissue state. The MIP nanosystem serves as an advanced information transfer system, allowing precise regulation of trained immunity, and offers a promising approach for effective liver fibrosis immunotherapy with the potential for clinical translation.

Enhanced Chemoradiotherapy for MRSA-Infected Osteomyelitis Using Immunomodulatory Polymer-Reinforced Nanotherapeutics.

The eradication of osteomyelitis caused by methicillin-resistant Staphylococcus aureus (MRSA) poses a significant challenge due to its development of biofilm-induced antibiotic resistance and impaired innate immunity, which often leads to frequent surgical failure. Here, the design, synthesis, and performance of X-ray-activated polymer-reinforced nanotherapeutics that modulate the immunological properties of infectious microenvironments to enhance chemoradiotherapy against multidrug-resistant bacterial deep-tissue infections are reported. Upon X-ray radiation, the proposed polymer-reinforced nanotherapeutic generates reactive oxygen species and reactive nitrogen species. To robustly eradicate MRSA biofilms at deep infection sites, these species can specifically bind to MRSA and penetrate biofilms for enhanced chemoradiotherapy treatment. X-ray-activated nanotherapeutics modulate the innate immunity of macrophages to prevent the recurrence of osteomyelitis. The remarkable anti-infection effects of these nanotherapeutics are validated using a rat osteomyelitis model. This study demonstrates the significant potential of a synergistic chemoradiotherapy and immunotherapy method for treating MRSA biofilm-infected osteomyelitis.

AGER1 deficiency-triggered ferroptosis drives fibrosis progression in nonalcoholic steatohepatitis with type 2 diabetes mellitus.

Hyperglycemia is an independent risk factor for the rapid progression of nonalcoholic steatohepatitis (NASH) to liver fibrosis with an incompletely defined mechanism. Ferroptosis is a novel form of programmed cell death that has been identified as a pathogenic mechanism in various diseases. However, the role of ferroptosis in the development of liver fibrosis in NASH with type 2 diabetes mellitus (T2DM) is unclear. Here, we observed the histopathological features of the progression of NASH to liver fibrosis as well as hepatocyte epithelial-mesenchymal transition (EMT) in a mouse model of NASH with T2DM and high-glucose-cultured steatotic human normal liver (LO2) cells. The distinctive features of ferroptosis, including iron overload, decreased antioxidant capacity, the accumulation of reactive oxygen species, and elevated lipid peroxidation products, were confirmed in vivo and in vitro. Liver fibrosis and hepatocyte EMT were markedly alleviated after treatment with the ferroptosis inhibitor ferrostatin-1. Furthermore, a decrease in the gene and protein levels of AGE receptor 1 (AGER1) was detected in the transition from NASH to liver fibrosis. Overexpression of AGER1 dramatically reversed hepatocyte EMT in high-glucose-cultured steatotic LO2 cells, whereas the knockdown of AGER1 had the opposite effect. The mechanisms underlying the phenotype appear to be associated with the inhibitory effects of AGER1 on ferroptosis, which is dependent on the regulation of sirtuin 4. Finally, in vivo adeno-associated virus-mediated AGER1 overexpression effectively relieved liver fibrosis in a murine model. Collectively, these findings suggest that ferroptosis participates in the pathogenesis of liver fibrosis in NASH with T2DM by promoting hepatocyte EMT. AGER1 could reverse hepatocyte EMT to ameliorate liver fibrosis by inhibiting ferroptosis. The results also suggest that AGER1 may be a potential therapeutic target for the treatment of liver fibrosis in patients with NASH with T2DM. Chronic hyperglycemia is associated with increased advanced glycation end products, resulting in the downregulation of AGER1. AGER1 deficiency downregulates Sirt4, which disturbs key regulators of ferroptosis (TFR-1, FTH, GPX4, and SLC7A11). These lead to increased iron uptake, decreasing the antioxidative capacity and enhanced lipid ROS production, ultimately leading to ferroptosis, which further promotes hepatocyte epithelial-mesenchymal transition and fibrosis progression in NASH with T2DM.

PKM2 promotes proinflammatory macrophage activation in ankylosing spondylitis.

Macrophages play a critical role in ankylosing spondylitis by promoting autoimmune tissue inflammation through various effector functions. The inflammatory potential of macrophages is highly influenced by their metabolic environment. Here, we demonstrate that glycolysis is linked to the proinflammatory activation of human blood monocyte-derived macrophages in ankylosing spondylitis. Specifically, ankylosing spondylitis macrophages produced excessive inflammation, including TNFα, IL1ß, and IL23, and displayed an overactive status by exhibiting stronger costimulatory signals, such as CD80, CD86, and HLA-DR. Moreover, we found that patient-derived monocyte-derived M1-type macrophages (M1 macrophages) exhibited intensified glycolysis, as evidenced by a higher extracellular acidification rate. Upregulation of PKM2 and GLUT1 was observed in ankylosing spondylitis-derived monocytes and monocyte-derived macrophages, especially in M1 macrophages, indicating glucose metabolic alteration in ankylosing spondylitis macrophages. To investigate the impact of glycolysis on macrophage inflammatory ability, we treated ankylosing spondylitis M1 macrophages with 2 inhibitors: 2-deoxy-D-glucose, a glycolysis inhibitor, and shikonin, a PKM2 inhibitor. Both inhibitors reduced proinflammatory function and reversed the overactive status of ankylosing spondylitis macrophages, suggesting their potential utility in treating the disease. These data place PKM2 at the crosstalk between glucose metabolic changes and the activation of inflammatory macrophages in patients with ankylosing spondylitis.

LINC01123 promotes immune escape by sponging miR-214-3p to regulate B7-H3 in head and neck squamous-cell carcinoma.

Numerous studies have shown that long noncoding RNAs (LncRNAs) are involved in the development and immune escape of head and neck squamous-cell carcinoma (HNSCC). However, the specific regulatory mechanisms by which LINC01123 regulates HNSCC and its correlation with immunity remain unclear. Therefore, this study's primary purpose was to explore the mechanisms by which LINC01123 regulates the immune escape and progression of HNSCC. This study confirmed that LINC01123 is competitively bound to miR-214-3p, and miR-214-3p specifically targets B7-H3. The effects of LINC01123, B7-H3, and miR-214-3p on tumor progression, CD8+T-cell-mediated immune response, and the tumorigenicity of HNSCC in vitro and in vivo were examined through the downregulation or upregulation of LINC01123, B7-H3, and miR-214-3p. Our results indicated that LINC01123 and B7-H3 were highly expressed in HNSCC and are associated with poor prognosis in patients. Notably, overexpression of LINC01123 or B7-H3 or downregulation of miR-214-3p inhibited the function of CD8+T cells and promoted the progression of HNSCC. Therefore, LINC01123 acts as a miR-214-3p sponge to inhibit the activation of CD8+T cells and promote the progression of HNSCC by upregulating B7-H3.

A Targeted Photosensitizer Mediated by Visible Light for Efficient Therapy of Bacterial Keratitis.

Bacterial keratitis is a serious bacterial infection of the cornea that can cause sight loss in severe cases because of the sharp decline of efficacious antibiotics. Herein, a targeted photosensitizer based on BODIPY severing as a photobactericidal agent was developed for treating bacterial keratitis. The water solubility of the material was as high as 10 mg/mL, which was attributable to the introduction of pathogen-targeting galactose and fucose. The photosensitizer was able to preferentially bind Pseudomonas aeruginosa instead of mammalian cells and trigger the aggregation of bacteria, which ultimately facilitated effective pathogen ablation upon the generation of reactive oxygen species (ROS) via laser irradiation. Photoexcited targeted photosensitizers can promote wound healing by eradicating P. aeruginosa in rat eyes and reducing the inflammatory response, thus exhibiting the significant therapeutic effect on bacterial keratitis. We also performed molecular level mechanistic studies using the unique field-induced droplet ionization mass spectrometry methodology and confirmed that the generated ROS were mainly singlet oxygen that caused lipid peroxidation (Type II mechanism). We anticipate that the targeted photosensitizer will have great potential in the application of clinical photodynamic therapy to ocular infection.

Diabetic ferroptosis plays an important role in triggering on inflammation in diabetic wound.

Impaired wound healing is a major complication of diabetes and involves sustained inflammation and oxidative stress at the wound site. Here, we investigated the potential involvement of ferroptosis, a newly discovered form of cell death characterized by iron-dependent accumulation of lipid peroxides in the pathogenesis of diabetic wound healing. Fibroblasts and vascular endothelial cells exposed to high glucose concentrations in vitro contained elevated levels of reactive oxygen species (ROS), lipid peroxidation products, and ferroptosis-associated proteins and displayed reduced survival and migration. These effects of high glucose were all significantly reduced by treatment with the ferroptosis inhibitor ferrostatin-1 (Fer-1). Similarly, in a rat model of diabetes, direct application of Fer-1 to the wound site reduced the expression of oxidative stress and inflammation markers and accelerated wound healing via activation of the anti-inflammatory phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway. Our results implicate ferroptosis in wound healing and identify a potential new therapeutic target for difficult-to-treat diabetic wounds.NEW & NOTEWORTHY Ferroptosis-related characteristic changes were found in diabetic wound models. Inhibition of ferroptosis improved inflammatory infiltration of diabetic wounds. PI3K/AKT signal pathway was rescued by restraining of ferroptosis. Mitigation of ferroptosis in diabetic wound promoted the wound healing.

Synergy between Clinical Microenvironment Targeted Nanoplatform and Near-Infrared Light Irradiation for Managing Pseudomonas aeruginosa Infections.

Chronic infections caused by Pseudomonas aeruginosa pose severe threats to human health. Traditional antibiotic therapy has lost its total supremacy in this battle. Here, nanoplatforms activated by the clinical microenvironment are developed to treat P. aeruginosa infection on the basis of dynamic borate ester bonds. In this design, the nanoplatforms expose targeted groups for bacterial capture after activation by an acidic infection microenvironment, resulting in directional transport delivery of the payload to bacteria. Subsequently, the production of hyperpyrexia and reactive oxygen species enhances antibacterial efficacy without systemic toxicity. Such a formulation with a diameter less than 200 nm can eliminate biofilm up to 75%, downregulate the level of cytokines, and finally promote lung repair. Collectively, the biomimetic design with phototherapy killing capability has the potential to be an alternative strategy against chronic infections caused by P. aeruginosa.

Oxygen Self-Supplying Nanotherapeutic for Mitigation of Tissue Hypoxia and Enhanced Photodynamic Therapy of Bacterial Keratitis.

Hypoxia, a common characteristic of bacterial infections, is known to be closely associated with the emergence of multidrug-resistant bacteria, which hastens the need to develop advanced microbicides and antibacterial techniques. Photodynamic therapy is a promising strategy to reduce bacterial antibiotic resistance and employs photosensitizers, excitation light sources, and sufficient oxygen to generate toxic reactive oxygen species (ROS). The inherent limitation of PDT is that the generation of ROS is restricted by the hypoxic microenvironment in infection sites. Here, an oxygen self-supplying nanotherapeutic is developed to enhance antibacterial activity against multidrug-resistant bacteria on the basis of fluorinated boron dipyrromethene (BODIPY)-based glycomimetics. The nanotherapeutic not only could capture the bacteria efficiently but also was able to act as an oxygen carrier to relieve the hypoxic microenvironment of bacterial infections, thus achieving enhanced PDT efficacy. In a Pseudomonas aeruginosa infection of a rat cornea, typical administration of the nanotherapeutic decreased the infiltrate and showed a faster healing capacity in comparison with BODIPY-based glycomimetics. Self-supplying oxygen nanotherapeutics that relieve the hypoxic microenvironment and interfere with bacterial colonization have been shown to be a promising candidate for the management of drug-resistant microbial keratitis.

Investigation and analysis of HEp 2 indirect immunofluorescence titers and patterns in various liver diseases.

INTRODUCTION: Antinuclear antibody (ANA) testing using indirect immunofluorescence assay (IIFA) is a common and economical method which contributes to detect systemic autoimmune diseases (SARD) and autoimmune liver diseases (AILD). The primary aim of our study was to investigate ANA positivity and their patterns in multiple liver diseases, including primary biliary cirrhosis (PBC), autoimmune hepatitis (AIH), hepatitis B virus infection (HBV), hepatitis C virus infection (HCV), and hepatic carcinoma (HCC). Besides, we also compared the ANA titers and patterns in patients with liver disease, SARD, and healthy controls (HC). METHODS: A total of 2537 patients with SARD, 137 PBC cases, 57 AIH cases, 3420 HBV cases, 769 HCV cases, 268 HCC cases, and 1073 HC were retrospectively assessed. The titers and patterns of ANA were detected with the IIFA method. RESULTS: ANA positivity rate was considerably discernible between these diseases, which is 90.1% in SARD, 93.4% in PBC, 49.1% in AIH, 19.1% in HBV, 13.9% in HCV, and 23.5% in HCC. Moreover, only 4.9% of HCC cases, 2.5% of HBV patients, and 1.6% of HCV patients had an ANA titer ≥ 1:320. The mixed pattern which composed of at least two patterns majorly lied in PBC. AC-15 and AC-21 was frequently related to liver diseases; the former pattern was more frequently found in AIH (84.2%) and PBC (8.8%), and the latter pattern was easily seen in PBC (62.2%) and HCC (22.6%). The positive rate of ANA in HC was 12.2%, and its major pattern was AC-2. CONCLUSIONS: There are differences in ANA positivity among patients with SARD and various liver diseases. Some mixed patterns may provide important evidence for the diagnosis of PBC. Clinicians should pay attention to ANA patterns and titer during the interpretation of this test. Key Points • Defining the clinical relevance of antinuclear antibody (ANA) using indirect immunofluorescence assay in the context of diseases can be an important tool for the clinician in the diagnostic work-up of patients with liver diseases. • The mixed pattern of ANA is majorly found in primary biliary cirrhosis (PBC). ANA patterns including AC-15 and AC-21 are frequently related to liver diseases. AC-15 is more often found in autoimmune hepatitis (AIH) (84.2%) and PBC (8.8%), and AC-21 is easily found in PBC (62.2%, and hepatic carcinoma (HCC) (22.6%). • ANA positivity can be seen in 19.1% of hepatitis B virus infection (HBV) cases, 13.9% of hepatitis C virus infection (HCV) cases, and 23.5% of HCC cases. Only 2.5% of HBV patients, 1.6% of HCV patients, and 4.9% of HCC cases have an ANA titer ≥ 1:320.

Glutamine Enhances the Hypoglycemic Effect of Insulin in L6 Cells via Phosphatidylinositol-3-Kinase (PI3K)/Protein Kinase B (AKT)/Glucose Transporter 4 (GLUT4) Signaling Pathway.

BACKGROUND Diabetes mellitus (DM) is characterized by a decreased blood level of glutamine (Gln), which may contribute to the disturbance in the effect of insulin on skeletal muscle. Therefore, it is crucial to study how to improve the effect of insulin on skeletal muscle by increasing Gln. In the present study, we investigated the effect of Gln on the hypoglycemic action of insulin in skeletal muscle L6 cells at high glucose levels through the insulin signaling pathway and glycogen synthesis pathway. MATERIAL AND METHODS The L6 cells were cultured in and stimulated by Gln and insulin. The glutamine analogue, L-Gamma-Glutamyl-p-nitroanilide (GPNA), was used for verifying the effect of Gln. The expression of insulin signaling molecules, including phosphatidylinositol-3-kinase (PI3K), 3-phosphoinositide-dependent protein kinase-1 (PDK1), protein kinase B (AKT), protein kinase C zeta (PKCz), and glucose transporter 4 (GLUT4), were detected by real-time PCR and Western blot analysis, GLUT4 translocation was observed by immunofluorescence staining, glycogen synthase kinase (GSK) was analyzed by Western blotting, and glucose uptake was measured by glucose oxidase method (GOD). RESULTS The results demonstrated that Gln combined with insulin remarkably up-regulated PI3K and PDK1 and also increased AKT and PKCz phosphorylation. The present study shows that Gln enhanced the impact of insulin on GLUT4 and its translocation. The results of glucose uptake and GSK phosphorylation further confirmed the hypoglycemic effect of Gln accompanied with insulin. The hypoglycemic effect of Gln was reversed by GPNA. CONCLUSIONS These findings suggest that Gln enhances the hypoglycemic role of insulin through the PI3K/AKT/GLUT4 signaling pathway and glycogen synthesis pathway.

Glucagon-like peptide-1 potentiates glucose-stimulated insulin secretion via the transient receptor potential melastatin 2 channel.

The transient receptor potential melastatin 2 (TRPM2) channel, a Ca2+ permeable channel activated by cAMP, is expressed on pancreatic ß-cells and is responsible for the regulation of insulin secretion. It is known that glucose-stimulated insulin secretion (GSIS) can be potentiated by glucagon like peptide-1 (GLP-1), and that the changes in the extracellular glucose concentration alter the levels of intracellular adenosine ATP and cAMP. The present study hypothesized that TRPM2 mediates the modulatory effect of GLP-1 on insulin secretion. The results demonstrated that silencing of TRPM2 eliminated GLP-1-enhanced insulin secretion, indicating the involvement of TRPM2 in this process. In addition, the results of current recordings of TRPM2 and measurement of the resulting insulin secretion in ß-cells in the presence of GLP-1 and various concentrations of glucose suggest that GLP-1 regulates GSIS via the TRPM2 channel. Furthermore, inhibiting the activity or expression of TRPM2 attenuated GLP-1-induced GSIS. By using specific activators or inhibitors, the present study demonstrated that the two primary downstream effectors of the GLP-1 receptor, exchange protein directly activated by cAMP and protein kinase A, differentially influence GSIS and GLP-1-potentiated GSIS. In conclusion, the present study revealed the role of TRPM2 in GLP-1-regulated insulin secretion. The results of the present study provide a novel avenue for the prevention and treatment of diabetes and its complications.

Preparation of a chlorophyll derivative and investigation of its photodynamic activities against cholangiocarcinoma.

Photodynamic therapy (PDT) is emerging as a promising method for the treatment of various cancer diseases. However, the clinical application of PDT is limited due to the lack of effective photosensitizers. In this study, a novel chlorophyll derivative, N,N-bis(2-carboxyethyl)pyropheophorbide a (BPPA), had been synthesized and characterized. BPPA had a characteristic long wavelength absorption peak at 669nm and a singlet oxygen quantum yield of 0.54. To investigate the photodynamic ability of BPPA against cholangiocarcinoma (CCA), cellular uptake, subcellular location and bio-distribution, in vitro and in vivo PDT efficacy of BPPA were studied. The results showed that BPPA could rapidly accumulate in QBC-939 cells and localize in the cytoplasm. BPPA- PDT was effective in reducing the cell viability in a drug dose- and light dose-dependent manner in vitro. In CCA xenograft nude mouse model, the concentration of BPPA in the plasma lowered rapidly, and the fluorescence signal peaked at 0.5h and 2h after injection in the skin and tumor, respectively. Significant quantities could be observed in the tumor. BPPA followed by irradiation could significantly inhibit growth of tumors, and histological examination revealed necrotic damage in PDT-treated tumors. These results suggested that BPPA could be a promising drug candidate for photodynamic therapy in cholangiocarcinoma.

An Acid-Triggered Degradable and Fluorescent Nanoscale Drug Delivery System with Enhanced Cytotoxicity to Cancer Cells.

To reduce side-effects of anticancer drugs, development of nanocarriers with precise biological functions is a critical requirement. In this study, the multifunctional nanoparticles combining imaging and therapy for tumor-targeted delivery of hydrophobic anticancer drugs were prepared via self-assembly of amphiphilic copolymers obtained using RAFT polymerization, specifically, acid-labile ortho ester and galactose. First, boron-dipyrromethene dye-conjugated chain transfer agent provides fluorescent imaging capability for diagnostic application. Second, nanoparticles were stable under physiological conditions but degraded in acidic tumor microenvironment, leading to enhanced anticancer efficacy. Third, the application of biocompatible glycopolymers efficiently increased the target-to-background ratio through carbohydrate-protein interactions. Data from cell viability, cellular internalization, flow cytometry, biodistribution and anticancer efficacy tests showed that the drug-loaded nanoparticles were capable of inhibiting cancer cell proliferation with significantly enhanced capacity. Our newly developed multifunctional nanoparticles may thus facilitate the development of effective drug delivery systems for application in diagnosis and therapy of cancer.

Antitumor effects evaluation of a novel porphyrin derivative in photodynamic therapy.

In this paper, the antitumor activity of a novel porphyrin-based photosensitizer 5,10,15,20-tetrakis[(5-diethylamino)pentyl] porphyrin (TDPP) was reported in vitro and in vivo. The photophysical and cellular properties of TDPP were investigated. The singlet oxygen generation quantum yield of TDPP was detected; it showed a high singlet oxygen quantum yield of 0.52. The intracellular distribution of photosensitizer was detected with laser scanning confocal microscopy. The efficiency of TDPP-photodynamic therapy (PDT) in vitro was analyzed by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and in situ trypan blue exclusion test. Treated with a 630-nm laser, TDPP can kill cultured human esophageal cancer cell line (Eca-109) cells and reduce the growth of Eca-109 xenograft tumors significantly in BABL/c nude mice. And histopathological study was also used to confirm the antitumor effect. It has the perspective to be developed as a new antitumor drug in photodynamic therapy and deserves further investigation.

Effect of Dental Pulp Stem Cells (DPSCs) in Repairing Rabbit Alveolar Bone Defect.

BACKGROUND: The aim of this research was to analyze the ability of dental pulp stem cells (DPSCs) in repairing rabbit alveolar bone defect. METHODS: First, DPSCs were isolated from the pulp tissue of the anterior teeth and molars of young rabbits and cultured in vitro. Subsequently, cell cloning efficiency, anti-vimentin, and anti-CD44 immunohistochemical staining were investigated. Second, bone defect models were made in rabbit alveolar toothless jaw. The bone defects in the control group were filled with 0.25 g bio-oss bone mixed with PBS solution, while the bone defects in the experimental group were filled with 0.25 g bio-oss bone mixed with 1 x 108 DPSCs/L. Animals were sacrificed six weeks after the surgery, the alveolar tissue was collected for paraffin sections, HE staining, and immunohistochemistry of bone sialoprotein (BSP). RESULTS: The immunocytochemistry results of surface markers showed a positive staining of vimentin and CD44 in the DPSCs forming low density colonies after inoculation. The alveolar tissue of the control group showed a small amount of erythrocytes highlighted by HE staining, with no visible new bone formation except for a few osteoblasts, with a weakly positive BSP immunohistochemical staining. HE staining in the experimental group showed that the inflammatory exudate was significantly absorbed, some new bone tissue was present, with many osteoblasts around the bone defects, and with a strong positive BSP immunohistochemical staining, which was statistically significant compared to the control group (p < 0.05). CONCLUSIONS: DPSCs possess the ability to differentiate into bone cells, promoting the repair and regeneration of alveolar bone defects.

A pH gated, glucose-sensitive nanoparticle based on worm-like mesoporous silica for controlled insulin release.

This study prepares a kind of core-shell hybrid nanoparticles, which is worm-like, pH gated, and glucose-sensitive. It has a mesoporous silica nanoparticle (MSN) core and polymer shell (cross-linked and non-cross-linked), bearing 3-acrylamidophenylboronic acid (AAPBA) and N-isopropylacrylamide (NIPAM) as sensor moieties. The shell of the nanoparticles has presented a distinct transition from swollen state to collapsed state as the temperature increases, which offers easy access to drug loading. Here, insulin is applied as a model drug and the behaviors of its loading/release are investigated. Insulin loading is up to 15% via mesoporous silica core. In vitro experiment shows that the cumulative release of insulin is dependent on glucose concentration, and the glucose sensitivity could be adjusted simply by different pH values. Simultaneously, compared with the non-cross-linked shell, the cross-linked shell, using dextran-maleic acid (Dex-Ma) as a macromolecule cross-link, enables insulin to release more persistently. Also, cell viability assay indicates that these nanoparticles have good biocompatibility. Consequently, the novel, pH gated, glucose-sensitive core-shell nanoparticles may have potential applications as a vehicle of self-regulated insulin delivery system.

Preparation of photosensitizer-loaded PLLA nanofibers and its anti-tumor effect for photodynamic therapy in vitro.

Photodynamic therapy (PDT) is a promising new treatment for cancer that has been recently accepted clinically. PDT is based on the administration of tumor-localizing photosensitizers (PSs), followed by exposing the neoplastic area to the light absorbed by the PS. In this article, a novel anticancer nanofiber membrane containing purpurin-18 (0.1%) was successfully prepared. The thickness of membrane was 0.028 mm, and the average fiber diameter was around 357 nm by scanning electron microscope (SEM). It was indicated that purpurin-18 possessed excellent compatibility with PLLA from FTIR spectrum. The physical properties of fiber membrane were also characterized by Differential Scanning Calorimetry (DSC) and X-ray diffraction (XRD). Cell morphology and the interaction between cells and nanofibers were studied by SEM. The results showed that both SMMC 7721 and ECA109 cells can adhere and spread on the surface of the polymer nanofiber, and both cells can interact and integrate well with the surrounding fibers. The efficacy of PDT was determined by MTT assays. The results showed that the cells were killed immediately after PDT and purpurin-18 had no different efficacy to different cancer cell lines. In summary, the PS-loaded PLLA nanofibers were prepared successfully, and the SMMC 7721 and ECA109 cells could be inhibited and killed through photodynamic therapy.

A hydrotropic ß-cyclodextrin grafted hyperbranched polyglycerol co-polymer for hydrophobic drug delivery.

The development of successful formulations for poorly water soluble drugs remains a longstanding, critical, and challenging issue in cancer therapy. A ß-cyclodextrin (CD) functionalized hyperbranched polyglycerol (HPG) has been prepared as a potential water insoluble drug carrier. The HPG-g-CD molecules could self-assemble into multimolecular spherical micelles in water, the size of which ranged from 200 to 300 nm, with good dispersity. A high loading capacity and high encapsulation efficiency of paclitaxel, as a model, were obtained. The release profiles of different co-polymer compositions showed a burst release followed by continuous extended release. Furthermore, MTT analysis showed that HPG-g-CD had good biocompatibility, indicating that HPG-g-CD may be considered a promising hydrophobic drug delivery system.

Gradient cross-linked biodegradable polyelectrolyte nanocapsules for intracellular protein drug delivery.

Gradient shell cross-linked hollow polyelectrolyte nanocapsules composed of cysteamine conjugated chitosan and dextran sulfate were prepared by layer-by-layer adsorption on beta-cyclodextrin (beta-CD) functionalized silica spheres followed by cross-linking thiols and removal of silica core. This disulfide bond gradient cross-linked nanocapsules combined reduction and pH sensitive. Gradually increased from the inside to the outside of the cross-linking degree, one purpose is to ensure that cross-linking disulfide bond after reduction cleavage still has pH sensitive, on the other hand is to avoid cross-linked contraction of internal damage the crystal and bioactivity of protein drugs. Disulfide cross-linked nanocapsules were used to enhance the physical stability against acidic pH conditions compared to the un-cross-linked ones. Bovine serum albumin, as a model protein drug, was loaded inside nanocapsules. The disulfide bond cross-linked nanocapsules are intended to remain more stable in physiological pH and decrease the loss of protein drugs caused by the gastric cavity, and can release the drugs in the intracellular environment after glutathione reduction.