Mechanically Tough and Regenerable Antibacterial Nanofibrillated Cellulose-Based Aerogels for Oil/Water Separation.

Nanofibrillated cellulose (NFC)-based aerogels have been widely used for various applications. However, the disadvantages of poor structural stability, low mechanical toughness, and easy contamination by bacteria hinder their large-scale application. In this work, 3-(3'-acrylicacidpropylester)-5,5-dimethyl hydantoin (APDMH) was grafted on oxidized NFC (ONC) to prepare antibacterial poly(APDMH)-g-ONC (PAC). PAC and poly(ethyleneimine) (PEI) were chemically cross-linked using 3-glycidoxypropyltrimethox (GPTMS), aiming at constructing a PAC-g-PEI aerogel with multiple network structures. The mechanical behaviors of composite aerogel and oil/water separation performances under different conditions were investigated. PAC-g-PEI aerogel exhibits outstanding fatigue resistance (>50 cycles of compression) and superior elasticity (96.76% height recovery after five compression-release cycles at 50% strain). The obtained superhydrophilic and underwater-oleophobic properties endow the aerogel with excellent oil/water separation performances, achieving a satisfactory separation efficiency of over 99% and flux of over 9500 L·m-2·h-1. Furthermore, the chlorinated aerogel of PAC-g-PEI-Cl shows highly efficient and rechargeable antibacterial properties, can inactivate 6.72-log Escherichia coli and 6.60-log Staphylococcus aureus within 10 min, and can still kill all inoculated bacteria after 50 cycles. In addition, PAC-g-PEI-Cl aerogel can inhibit biofilm formation, making it a promising candidate for highly efficient oil/water separation applications in diverse harsh conditions.

Charge Reversible and Mitochondria/Nucleus Dual Target Lipid Hybrid Nanoparticles To Enhance Antitumor Activity of Doxorubicin.

The experiment aims to increase antitumor activity while decreasing the systemic toxicity of doxorubicin (DOX). Charge reversible and mitochondria/nucleus dual target lipid hybrid nanoparticles (LNPs) was prepared. The in vitro experimental results indicated that LNPs released more amount of DOX in acidic environment and delivered more amount of DOX to the mitochondria and nucleus of tumor cells than did free DOX, which resulted in the reduction of mitochondrial membrane potential and the enhancement of cytotoxicity of LNPs on tumor cells. Furthermore, the in vivo experimental results indicated that LNPs delivered more DOX to tumor tissue and significantly prolonged the retention time of DOX in tumor tissue as compared with free DOX, which consequently resulted in the high antitumor activity and low systemic toxicity of LNPs on tumor-bearing nude mice. The above results indicated that charge reversible mitochondria/nucleus dual targeted lipid hybrid nanoparticles greatly enhanced therapeutic efficacy of DOX for treating lung cancer.

[Clinicopathological Analysis of Autoimmune Hepatitis with Sjögren's Syndrome].

OBJECTIVE: To explore the biochemical-immune and pathological characteristics of autoimmune hepatitis (AIH) with Sjögren's syndrome (SS) . METHODS: A total of 76 cases of AIH patients were included from January 2009 to April 2017. Among them,there were 40 cases of AIH with SS and 36 cases without SS. The liver function,immunological index,histological features,length of first diagnosis and treatment costs were compared between the two groups. RESULTS: For AIH+SS group and AIH group,the proportion of women were 97.5% and 77.8%,the proportion of the first diagnosis age less than 60 years were 70% and 47.2%,the median course of disease were 30 months and 9 months,all the difference were statistically significant (P<0.05). The chief complaints in AIH+SS group and AIH group were as follows: cutaneous or scleracterus (52.5% vs. 38.9%),abnormal transaminase (17.5% vs. 44.4%),dryness of mouth and eye (15.0% vs. 2.8%),all the difference were statistically significant (P<0.05). There were no statistically significant difference in hospitalization expenses,and length of stay between the two groups (P>0.05). The median level of total bilirubin (TBIL),direct bilirubin (DBIL) and immunoglobulin (Ig) M of AIH +SS group were higher than those of AIH group,the mean level of albumin (ALB) and complement 3 (C3) of AIH +SS group were lower than those of AIH group,and the positive rate of anti-mitochondrial antibody-M2 (AMA-M2) ,anti-Ro antibody A (SSA),anti-La antibody (SSB) and anti-soluble liver antigen antibody (SLA) of AIH+SS group were higher than those of AIH group (P<0.05). There were no statistically significant difference in histological changes of hepatocytes and bile duct injury rate (P>0.05). CONCLUSION: AIH patients in young and middle-aged women need to be vigilant with SS with main manifestation of skin sclera and high specific autoantibodies positive.

Mitochondria and Nucleus Dual Delivery System To Overcome DOX Resistance.

Doxorubicin (DOX) is a broad-spectrum chemotherapy drug to treat tumors. However, severe side effects and development of DOX resistance hinder its clinical application. In order to overcome DOX resistance, DOX/TPP-DOX@Pasp-hyd-PEG-FA micelles were prepared by using newly synthesized comb-like amphiphilic material Pasp-hyd-PEG-FA. Drug released in vitro from micelles showed a pH-dependent manner. DOX/TPP-DOX@Pasp-hyd-PEG-FA induced more apoptosis in KB cell and MCF-7/ADR cell than DOX@Pasp-hyd-PEG-FA. Confocal laser scanning microscopy experiment indicated that DOX/TPP-DOX@Pasp-hyd-PEG-FA delivered TPP-DOX and DOX to the nucleus and mitochondria of the tumor cell simultaneously. Thus, DOX/TPP-DOX@Pasp-hyd-PEG-FA could significantly damage the mitochondrial membrane potential. DOX/TPP-DOX@Pasp-hyd-PEG-FA markedly shrinked the tumor volume in tumor-bearing nude mice grafted with MCF-7/ADR cell as compared with the same dose of free DOX. DOX was mainly accumulated in tumor tissue after DOX/TPP-DOX@Pasp-hyd-PEG-FA was injected to tumor-bearing nude mice by tail vein. After free DOX was injected to tumor-bearing nude mice by tail vein, DOX widely distributed through the whole body. Therefore, mitochondria and nucleus dual delivery system has potential in overcoming DOX resistance.

Poly lactic-co-glycolic acid controlled delivery of disulfiram to target liver cancer stem-like cells.

Disulfiram (DS), an anti-alcoholism drug, shows very strong cytotoxicity in many cancer types. However its clinical application in cancer treatment is limited by the very short half-life in the bloodstream. In this study, we developed a poly lactic-co-glycolic acid (PLGA)-encapsulated DS protecting DS from the degradation in the bloodstream. The newly developed DS-PLGA was characterized. The DS-PLGA has very satisfactory encapsulation efficiency, drug-loading content and controlled release rate in vitro. PLGA encapsulation extended the half-life of DS from shorter than 2minutes to 7hours in serum. In combination with copper, DS-PLGA significantly inhibited the liver cancer stem cell population. CI-isobologram showed a remarkable synergistic cytotoxicity between DS-PLGA and 5-FU or sorafenib. It also demonstrated very promising anticancer efficacy and antimetastatic effect in liver cancer mouse model. Both DS and PLGA are FDA approved products for clinical application. Our study may lead to repositioning of DS into liver cancer treatment.

Reduction of metal artifacts from alloy hip prostheses in computer tomography.

OBJECTIVE: The objective of this study was to evaluate the feasibility of reducing artifacts from large metal implants with gemstone spectral imaging (GSI) and metal artifact reduction software (MARS). METHODS: Twenty-three in-vivo cobalt-chromium-molybdenum alloy total hip prostheses were prospectively scanned by fast kV-switching GSI between 80 and 140 kVp. The computed tomography images were reconstructed with monochromatic energy and with/without MARS. Both subjective and objective measurements were performed to assess the severity of metal artifacts. RESULTS: Increasing photon energy was associated with reduced metal artifacts in GSI images (P < 0.001). Combination of GSI with MARS further diminished the metal artifacts (P < 0.001). Artifact reduction at 3 anatomical levels (femoral head, neck, and shaft) were evaluated, with data showing that GSI and MARS could reduce metal artifacts at all 3 levels (P = 0.011, P < 0.001, and P = 0.003, respectively). Nevertheless, in certain cases, GSI without MARS produced more realistic images for the clinical situation. CONCLUSIONS: Proper usage of GSI with/without MARS could reduce the computed tomography artifacts of large metal parts and improve the radiological evaluation of postarthroplasty patients.

[Selective Laser Sintering-produced porous titanium alloy scaffold for bone tissue engineering].

OBJECTIVE: To evaluate the biocompatibility of SLS-produced titanium alloy scaffold in vitro and investigate the therapeutic effects in repairing segmental bone defects. METHODS: Porous titanium alloy scaffolds were produced by SLS and their surfaces were either left untreated or acid etched. In vitro, mouse pre-osteoblasts (MC3T3-E1 cells) were cultured on these 2 group scaffolds, and then cell proliferation and differentiation were examined after cell seeding. In vivo, bone defects were artificially made in 15 New Zealand rabbits and the porous titanium specimens were implanted into the radius of rabbits for 3 months. The regulating checks of X-ray were determined. The osteointegration of the implants was investigated by Micro-CT and histological examination at 12 weeks after surgery. RESULTS: A gradual increase in cell-specific ALP synthesis by cells cultured in both groups was observed with longer culture time (14 d). ALP activity did not differ significantly between two groups (0.834 ± 0.092 vs 0.815 ± 0.081, P > 0.05) . Both Micro-CT and the histological analysis indicated that the titanium alloy scaffolds had excellent ability to facilitate the osteointegration in vivo. The results were significantly different between the empty control and the 2 different surface modifications of SLS-implants (25.4% ± 4.2% vs 23.6% ± 8.4% vs 12.3% ± 4.7%, P < 0.05). Between the groups with implants, the number of bone points was not significantly different, irrespective of the surface treatment (25.4% ± 4.2% vs 23.6% ± 8.4%, P > 0.05). CONCLUSION: Selective Laser Sintering-Produced porous titanium alloy scaffold possessed admirable biocompatibility in vitro. It also could be contributed to the healing of long tulular bone defect. The porous Ti6Al4V implant not only reduced the stress-shielding but also exerted appropriate osteoconductive properties.

Comparison of drug-coated balloon angioplasty versus common balloon angioplasty for arteriovenous fistula stenosis: A systematic review and meta-analysis.

Drug-coated balloons (DCBs) have been used in dialysis patients with arteriovenous fistula (AVF) stenosis, but whether DCBs have advantages over ordinary balloons is still controversial. A meta-analysis was designed to investigate the safety and efficacy of DCBs and common balloons (CBs) in the treatment of AVF stenosis. We searched the PubMed, EMBASE, and China National Knowledge Internet (CNKI) databases for randomized controlled trials that evaluated the comparison of DCB angioplasty versus CB angioplasty for AVF stenosis in dialysis patients and reported at least one outcome of interest. The results showed that the DCB group had a higher first-stage patency rate of the target lesion 6 months [odds ratio, OR = 2.31, 95% confidence interval, CI: (1.69, 3.15), p < .01] and 12 months [OR = 2.09, 95% CI: (1.50, 2.91), p < .01] after surgery. There was no statistically significant difference in all-cause mortality between the two groups at 6 months [OR = 0.85, 95% CI: (0.47, 1.52), p = .58] and 12 months [OR = 0.99, 95% CI: (0.60, 1.64), p = .97]. Compared with CB, DCBs as a new endovascular treatment for AVF stenosis have a higher primary patency rate of target lesions and can delay the occurrence of restenosis. There is no evidence that DCB can increase the mortality of patients.

Changes in bone density and cyst volume after marsupialization of mandibular odontogenic keratocysts (keratocystic odontogenic tumors).

PURPOSE: To evaluate bone formation after marsupialization of odontogenic keratocysts (keratocystic odontogenic tumors) of the mandible. PATIENTS AND METHODS: A total of 53 patients with mandibular odontogenic keratocysts underwent marsupialization. Clinical and radiographic examinations were done at 1, 3, and 6 months postoperatively. The bone density of the cyst site was measured on the panoramic radiographs using the Digora. The volume of the cyst was measured by injection of saline solution into the cyst cavity. Student t test and Spearman's rank correlation were used for statistical analysis. RESULTS: Healing was uneventful in all patients. The diameter of the cysts was 4.1 to 11.0 cm (average 5.4). The panoramic radiographs showed a continuous increase in bone density of the cystic area, with a 22.42% increase at 1 month, 46.07% at 3 months, and 64.69% at 6 months postoperatively compared with the preoperative values. The decrease in cyst volume was 19.05% at 1 month, 55.62% at 3 months, and 79.67% at 6 months postoperatively. The increase in bone density and decrease in cyst volume were more significant in the first 3 months than in second 3 months (P < .01). The increase in bone density correlated inversely with the decrease in the cyst volume (P < .01). CONCLUSION: Bone regeneration can occur more rapidly in large mandibular odontogenic keratocysts after marsupialization with drainage by a cyst plug. After 3 months, secondary enucleation of the cyst can be performed.

Bone-Targeted Calcium Phosphate-Polymer Hybrid Nanoparticle Co-Deliver Zoledronate and Docetaxel to Treat Bone Metastasis of Prostate Cancer.

Prostate cancer is the most common malignant tumor with bone metastasis, and there is still no ideal treatment for bone metastasis of prostate cancer. In this study, a pH and GSH dual sensitive calcium phosphate-polymer hybrid nanoparticle (DTX@Cap/HP) was prepared to co-deliver zoledronate (ZOL) and docetaxel (DTX) to treat bone metastasis of prostate cancer. DTX@Cap/HP exhibited high bone binding affinity and released more DTX and ZOL in acidic and high GSH concentration environment. A large amount of DTX@Cap/HP was uptaken by PC-3 cell in acidic medium than that in neutral medium. DTX@Cap/HP obviously reduced PC-3 cell proliferation and bone lesion in in-vitro 3D model of bone metastases of prostate cancer. Besides, DTX@Cap/HP also exhibited stronger anti bone metastases of prostate cancer activity in vivo as compared with the same dose of DTX + ZOL, which resulted from the co-delivery of DTX and ZOL to bone metastases of prostate cancer by DTX@Cap/HP and the synergistic effects of DTX and ZOL. DTX@Cap/HP has great potential in the treatment of bone metastases of prostate cancer.

Pilocarpine induces the residual secretion of salivary fluid in perfused submandibular glands of rats.

Pilocarpine is an M3 muscarinic agonist that is widely used for the treatment of xerostomia caused by various diseases and medical conditions. Pilocarpine induced the secretion of salivary fluid in perfused submandibular glands of rats. The secretion of salivary fluid observed after removal of pilocarpine was referred to as residual fluid secretion. The volume of fluid and time of the residual secretion depended on the dose of pilocarpine. Such a residual effect of pilocarpine was observed on fluid secretion via the paracellular pathway and oxygen consumption. When a muscarinic antagonist was added to the perfusate immediately after cessation of pilocarpine, residual secretion of salivary fluid did not occur. These observations indicate that the residual secretion of salivary fluid is a characteristics of the interaction of pilocarpine with muscarinic receptors.

Mitochondria and nucleus delivery of active form of 10-hydroxycamptothecin with dual shell to precisely treat colorectal cancer.

AIM: The objective of this study was to deliver a ring-closed form of 10-hydroxycamptothecin (HCPT) to the mitochondria and nucleus to treat colorectal cancer. MATERIALS & METHODS: HCPT-loaded nanoparticle HCPT@PLGA-PEG2k-triphenylphosphonium/PLGA-hyd-PEG4k-folic acid (PT/PHF) and HCPT@PT/PLGA-SS-PEG4k-folic acid (PSF) were prepared by using emulsion-solvent evaporation method. RESULTS: In vitro experimental results indicated HCPT@PT/PHF and HCPT@PT/PSF maintained a large amount of HCPT in active form, and delivered more HCPT to the nucleus and mitochondria of the tumor cell, which resulted in the enhancement of cytotoxicity of HCPT. In vivo experimental results indicated that HCPT@PT/PHF and HCPT@PT/PSF delivered more ring-closed form of HCPT to tumor tissue, which led to strong antitumor activity. CONCLUSION: HCPT@PT/PHF and HCPT@PT/PSF could enhance therapeutic efficacy of HCPT to colorectal cancer.

Enhanced fluorescent intensity of magnetic-fluorescent bifunctional PLGA microspheres based on Janus electrospraying for bioapplication.

Microspheres with magnetic-fluorescent functions have received attention due to fluorescent tracking and target positioning. To improve the accuracy of optical imaging and the fluorescent tracking of drug release, it is essential to enhance the fluorescent intensity of microparticles. Magnetic-fluorescent bifunctional poly lactic-co-glycolic acid (PLGA) Janus microspheres [PLGA/TbLa3(Bim)12]//[PLGA/Fe3O4] with double chambers were fabricated with the double-needle electrospraying method. The fluorescent drug TbLa3(Bim)12 with dual rare earth ions was encapsulated in one chamber, while Fe3O4 magnetic nanoparticles (Fe3O4 MNPs) were simultaneously encapsulated in another chamber. In comparison, magnetic-fluorescent PLGA composite microspheres PLGA/TbLa3(Bim)12/Fe3O4 were also prepared, which encapsulated fluorescent drugs TbLa3(Bim)12 with dual rare earth (RE) ions and Fe3O4 MNPs in one chamber. The fluorescent intensity at 542 nm of Janus microspheres was about three times higher than that of composite microspheres due to a decrease in contact between fluorescent-labeling RE drug and MNPs. The fluorescent intensities of Janus microspheres with different contents of Fe3O4 MNPs and TbLa3(Bim)12 were investigated. Furthermore, the magnetic properties, thermostability, cell toxicity and hemolytic properties of Janus microspheres were also assayed to conduct a tentative exploration of their bioapplication. The Janus microspheres provide many opportunities for application in biofields such as drug delivery.

Construction and optimization of pH-sensitive nanoparticle delivery system containing PLGA and UCCs-2 for targeted treatment of Helicobacter pylori.

The acidic environment of the stomach is a threat to the curative effect of antimicrobial drugs for the eradication of Helicobacter pylori (H. pylori) in the infected area. The conventional clinical formulations of antibiotics have low specificity to H. pylori, which disrupts the normal balance of intestinal microbiomes. Therefore, oral drug delivery system with better stability at low pH as well as higher specificity to target H. pylori would provide more effective strategy to eradicate H. pylori and reduce the side effect of antibiotics. Based on the construction of UreI-mediated targeted drug delivery system developed by our group, in this work, using urea-modified UCCs-2 as targeting moiety to the UreI channel protein which is specifically expressed on H. pylori, pH-sensitive amoxicillin-loaded AMX-PLGA/UCCs-2 nanoparticles produced by UCCs-2 and PLGA for targeted treatment of H. pylori infection were established. The nanoparticles were prepared by double emulsion-solvent evaporation method. To achieve a promising drug delivery system with favorable pH-sensitive properties, we adopted an orthogonal design to obtain the optimal formulation. The results showed that the optimized AMX-PLGA/UCCs-2 nanoparticles were in a favorable pH sensitive manner and exhibited low cytotoxicity, higher specificity and better anti-H. pylori efficiency than amoxicillin and non-targeting AMX-PLGA/Cs nanoparticle both in vitro and in vivo, which can protect the antimicrobial drugs against acidic environment and deliver them to targeted eradicate H. pylori in the infected location. The cellular uptake mechanism showed that AMX-PLGA/UCCs-2 nanoparticles are an effective UreI-mediated targeted drug delivery system for anti-H. pylori treatment, which can also be used as promising nanocarriers for oral delivery of other therapeutic drugs to targeted treat H. pylori.

[Clinical evaluation of the zirconia all ceramic crowns in 40 consecutive patients].

PURPOSE: To investigate clinical application, aesthetics, stability and bio-compatibility of zirconia all-ceramic crowns in prosthodontic patients. METHODS: Computer aided design and manufacturing techniques were used to make zirconia all ceramic crowns in 40 patients. They were divided into 2 groups according to the thickness of the gingival thickness. After 12 months of clinical observation, the aesthetics, stability, and bio-compatibility were evaluated by the crown color, crown edge fitness, losing ratio and gingival health. The data were analyzed using SPSS 13.0 software package. RESULTS: Slight marginal discrepancy was observed in 2 zirconia all ceramic crowns, no evidence of decay was observed at 1 year. CONCLUSIONS: Zirconia all ceramic crowns have a low fracture rate, good biological properties and excellent esthetic properties. It is ideal esthetic prosthesis.

Efficacy and Safety of Ologen Implant Versus Mitomycin C in Primary Trabeculectomy: A Meta-analysis of Randomized Clinical Trials.

PURPOSE: To assess the efficacy and safety of trabeculectomy with Ologen implant versus trabeculectomy with mitomycin C (MMC) for treatment of glaucoma. PATIENTS AND METHODS: Medline, EMBASE, Web of Science, Cochrane Central Register of Controlled Trials, and Google Scholar were searched for relevant randomized controlled trials. The outcome measures of efficacy were intraocular pressure and glaucoma medications reductions, and success rate. Safety estimates were measured by relative ratio for complications. RESULTS: A total of 6 studies including 224 participants were included in this meta-analysis. Ologen implant was associated with a numerically lower but nonsignificant percentage reduction in IOP compared with MMC. The pooled absolute IOP decreases from baseline (95% confidence interval) were: 13.28 mm Hg (11.33-15.23 mm Hg) versus 15.8 mm Hg (13.21-18.38 mm Hg) at 1 month; 12.95 mm Hg (11.45-14.44 mm Hg) versus 13.87 mm Hg (11.77-15.97 mm Hg) at 3 months; 11.44 mm Hg (8.77-14.11 mm Hg) versus 13.34 mm Hg (11.48-15.20 mm Hg) at 6 months; 10.05 mm Hg (7.14-12.96 mm Hg) versus 11.59 mm Hg (10.27-12.91 mm Hg) at 12 months; and 12.17 mm Hg (8.88-15.47 mm Hg) versus 10.64 mm Hg (8.15-13.12 mm Hg) at 24 months for Ologen implant versus MMC, respectively. There was no significant difference in the reduction in glaucoma medications, success rate, and incidence of complications. CONCLUSIONS: Trabeculectomy with an Ologen implant is comparable to the use of MMC with a similar long-term success rate. However, it does not seem to offer significant advantages of avoiding the potential complications related to MMC.

Doxorubicin-poly (ethylene glycol)-alendronate self-assembled micelles for targeted therapy of bone metastatic cancer.

In order to increase the therapeutic effect of doxorubicin (DOX) on bone metastases, a multifunctional micelle was developed by combining pH-sensitive characteristics with bone active targeting capacity. The DOX loaded micelle was self-assembled by using doxorubicin-poly (ethylene glycol)-alendronate (DOX-hyd-PEG-ALN) as an amphiphilic material. The size and drug loading of DOX loaded DOX-hyd-PEG-ALN micelle was 114 nm and 24.3%. In pH 5.0 phosphate buffer solution (PBS), the micelle released DOX significantly faster than in pH 7.4 PBS. In addition, with the increase of incubation time, more red DOX fluorescence was observed in tumor cells and trafficked from cytoplasm to nucleus. The IC50 of DOX loaded DOX-hyd-PEG-ALN micelle on A549 cells was obviously lower than that of free DOX in 48 h. Furthermore, the in vivo image experimental results indicated that a larger amount of DOX was accumulated in the bone metastatic tumor tissue after DOX loaded DOX-hyd-PEG-ALN micelle was intravenously administered, which was confirmed by histological analysis. Finally, DOX loaded DOX-hyd-PEG-ALN micelle effectively delayed the tumor growth, decreased the bone loss and reduced the cardiac toxicity in tumor-bearing nude mice as compared with free DOX. In conclusion, DOX loaded DOX-hyd-PEG-ALN micelle had potential in treating bone metastatic tumor.

Cellular uptake and antitumor activity of DOX-hyd-PEG-FA nanoparticles.

A PEG-based, folate mediated, active tumor targeting drug delivery system using DOX-hyd-PEG-FA nanoparticles (NPs) were prepared. DOX-hyd-PEG-FA NPs showed a significantly faster DOX release in pH 5.0 medium than in pH 7.4 medium. Compared with DOX-hyd-PEG NPs, DOX-hyd-PEG-FA NPs increased the intracellular accumulation of DOX and showed a DOX translocation from lysosomes to nucleus. The cytotoxicity of DOX-hyd-PEG-FA NPs on KB cells was much higher than that of free DOX, DOX-ami-PEG-FA NPs and DOX-hyd-PEG NPs. The cytotoxicity of DOX-hyd-PEG-FA NPs on KB cells was attenuated in the presence of exogenous folic acid. The IC50 of DOX-hyd-PEG-FA NPs and DOX-hyd-PEG NPs on A549 cells showed no significant difference. After DOX-hyd-PEG-FA NPs were intravenously administered, the amount of DOX distributed in tumor tissue was significantly increased, while the amount of DOX distributed in heart was greatly decreased as compared with free DOX. Compared with free DOX, NPs yielded improved survival rate, prolonged life span, delayed tumor growth and reduced the cardiotoxicity in tumor bearing mice model. These results indicated that the acid sensitivity, passive and active tumor targeting abilities were likely to act synergistically to enhance the drug delivery efficiency of DOX-hyd-PEG-FA NPs. Therefore, DOX-hyd-PEG-FA NPs are a promising drug delivery system for targeted cancer therapy.

Osteocompatibility evaluation of poly(glycine ethyl ester-co-alanine ethyl ester)phosphazene with honeycomb-patterned surface topography.

Biodegradable amino acid ester-substituted polyphosphazenes are unique biomaterials for tissue engineering. Considering the surface properties as topography and chemical composition having vital roles in regulating cellular response, in this study, a kind of micropatterned polyphosphazene films were prepared and subjected to osteoblasts culture. Briefly, poly(glycine ethyl ester-co-alanine ethyl ester)phosphazene (PGAP) was synthesized, and its solution in chloroform was cast under high (80%) or low (20%) environmental humidity. Honeycomb-patterned or flat PGAP films were resulted. By analyzing with scanning electron microscope, atomic force microscope, X-ray photoelectron spectroscope, and water contact angle measurement, the honeycomb-patterned PGAP films demonstrated higher surface roughness, phosphorous and nitrogen content, and hydrophilicity than the flat one. Although the initial cell attachment and proliferation on PGAP films were inferior to those on conventional poly(lactic-co-glycolic acid) films, P-containing PGAP was a sort of bone-binding bioactive polymer. With these alternations, honeycomb-patterned PGAP films had accordingly enhanced protein adsorption and apatite deposition in simulated body fluid and showed great advantages in promoting osteogenous differentiation. The results suggested a potential way to make polyphosphazenes as good choices for bone tissue regeneration by increasing their surface roughness and phosphorous content.