Self-Assembled Polymeric Micellar Nanoparticles as Nanocarriers for Poorly Soluble Anticancer Drug Ethaselen

A series of monomethoxy poly(ethylene glycol)-poly(lactide) (mPEG-PLA) diblock copolymers were synthesized, and mPEG-PLA micelle was fabricated and used as a nanocarrier for solubilization and delivery of a promising anticancer drug ethaselen. Ethaselen was efficiently encapsulated into the micelles by the dialysis method, and the solubility of ethaselen in water was remarkably increased up to 82 μg/mL before freeze-drying. The mean diameter of ethaselen-loaded micelles ranged from 51 to 98 nm with a narrow size distribution and depended on the length of PLA block. In vitro hemolysis study indicated that mPEG-PLA copolymers and ethaselen-loaded polymeric micelles had no hemolytic effect on the erythrocyte. The enhanced antitumor efficacy and reduced toxic effect of ethaselen-loaded polymeric micelle when compared with ethaselen-HP-β-CD inclusion were observed at the same dose in H22human liver cancer cell bearing mouse models. These suggested that mPEG-PLA polymeric micelle nanoparticles had great potential as nanocarriers for effective solubilization of poorly soluble ethaselen and further reducing side effects and toxicities of the drug

MRl of Prostate Cancer Antigen Expression for Diagnosis and lmmunotherapy

BACKGROUND: Tumor antigen (TA)-targeted monoclonal antibody (mAb) immunotherapy can be effective for the treatment of a broad range of cancer etiologies; however, these approaches have demonstrated variable clinical efficacy for the treatment of patients with prostate cancer (PCa). An obstacle currently impeding translational progress has been the inability to quantify the mAb dose that reaches the tumor site and binds to the targeted TAs. The coupling of mAb to nanoparticle-based magnetic resonance imaging (MRI) probes should permit in vivo measurement of patient-specific biodistributions; these measurements could facilitate future development of novel dosimetry paradigms wherein mAb dose is titrated to optimize outcomes for individual patients. METHODS: The prostate stem cell antigen (PSCA) is broadly expressed on the surface of prostate cancer (PCa) cells. Anti-human PSCA monoclonal antibodies (mAb 7F5) were bound to Au/Fe(3)O(4) (GoldMag) nanoparticles (mAb 7F5@GoldMag) to serve as PSCA-specific theragnostic MRI probe permitting visualization of mAb biodistribution in vivo. First, the antibody immobilization efficiency of the GoldMag particles and the efficacy for PSCA-specific binding was assessed. Next, PC-3 (prostate cancer with PSCA over-expression) and SMMC-7721 (hepatoma cells without PSCA expression) tumor-bearing mice were injected with mAb 7F5@GoldMag for MRI. MRI probe biodistributions were assessed at increasing time intervals post-infusion; therapy response was evaluated with serial tumor volume measurements. RESULTS: Targeted binding of the mAb 7F5@GoldMag probes to PC-3 cells was verified using optical images and MRI; selective binding was not observed for SMMC-7721 tumors. The immunotherapeutic efficacy of the mAb 7F5@GoldMag in PC-3 tumor-bearing mice was verified with significant inhibition of tumor growth compared to untreated control animals. CONCLUSION: Our promising results suggest the feasibility of using mAb 7F5@GoldMag probes as a novel paradigm for the detection and immunotherapeutic treatment of PCa. We optimistically anticipate that the approaches have the potential to be translated into the clinical settings

Optimal Economic Operation of Islanded Microgrid by Using a Modified PSO Algorithm

An optimal economic operation method is presented to attain a joint-optimization of cost reduction and operation strategy for islanded microgrid, which includes renewable energy source, the diesel generator, and battery storage system. The optimization objective is to minimize the overall generating cost involving depreciation cost, operation cost, emission cost, and economic subsidy available for renewable energy source, while satisfying various equality and inequality constraints. A novel dynamic optimization process is proposed based on two different operation control modes where diesel generator or battery storage acts as the master unit to maintain the system frequency and voltage stability, and a modified particle swarm optimization algorithm is applied to get faster solution to the practical economic operation problem of islanded microgrid. With the example system of an actual islanded microgrid in Dongao Island, China, the proposed models, dynamic optimization strategy, and solution algorithm are verified and the influences of different operation strategies and optimization algorithms on the economic operation are discussed. The results achieved demonstrate the effectiveness and feasibility of the proposed method

Efficacy and safety of secukinumab in active rheumatoid arthritis with an inadequate response to tumor necrosis factor inhibitors : a meta-analysis of phase III randomized controlled trials

Objectives: To address the efficacy and safety of secukinumab in comparison with placebo in active rheumatoid arthritis (RA) patients who had an inadequate response to tumor necrosis factor (TNF) inhibitors. Methods: Databases of PubMed, Embase, and Web of Science were searched to identify the relevant randomized controlled trials (RCTs). Risk ratio (RR) and 95% confidence interval (95% CI) were calculated with the Mantel–Haenszel random effects method. Statistical heterogeneity was assessed using the Cochran Q and I 2 tests. Results: A total of 1292 patients from three phase III RCT studies were included. Compared with placebo, secukinumab 150 mg was superior at 24 weeks in terms of ACR20 with RR (1.66, 95% CI 1.33, 2.08; P < 0.0001; I 2 = 0%), ACR50 (1.88, 95% CI 1.29, 2.72; P = 0.0009; I 2 = 0%), and ACR70 (2.15, 95% CI 1.15, 4.02; P = 0.02; I 2 = 0%). Consistent effects were also observed in pooled group of 150 mg and 75 mg secukinumab. For secukinumab 75 mg alone, ACR20 response rate was significantly higher compared with placebo (RR 1.62, 95% CI 1.29, 2.03; P < 0.00001; I 2 = 0%). Although ACR50 and ACR70 response rates showed a favorable trend to be higher, no statistical difference was observed (RR 1.68, 95% CI 0.99, 2.85, P = 0.05, I 2 = 47%; RR 1.81, 95% CI 0.78, 4.21, P = 0.17, I 2 = 34%, respectively). Compared with the placebo group, there was no increased risk of adverse effects (AEs) and serious AEs at 16 weeks in the pooled secukinumab group. Conclusions: In active RA patients with an inadequate response to TNF inhibitors, secukinumab may be a therapeutic option. Secukinumab 150 mg showed significantly better clinical efficacy with no increased risk of AEs and serious AEs compared with placebo. Trial registration: Clinical Trials.gov identifier: NCT01770379, NCT01350804, NCT01377012 Key Points• Secukinumab 150 mg showed significantly better clinical efficacy in active RA patients with an inadequate response to TNF inhibitors.• No increased risk of AEs and serious AEs in secukinumab group compared with placebo

Price-based response strategy of micro-energy-grid in energy-anciliary service markets

Under the reform of China’s power market, micro-energy-grid further enhances its own profitability by participating in the joint dispatch of energy trading and frequency regulation ancillary services. Aiming at the operation characteristics of multi-energy complementary, this paper proposes a price-based response strategy of micro-energy grid with different scenarios in the joint dispatch considering both energy trading and frequency regulation ancillary services. The dispatch structure and process of the micro-energy-grid are firstly proposed, following with the day-ahead economic dispatch strategy, intra-day optimization rolling strategy and real-time frequency regulation mileage allocation strategy. Finally, the cases study shows that the multi-energy response strategy closely follows the price fluctuations of power spot market, with the deviation energy and total energy cost respectively reducing by 17.34% and 19.61% through energy trading and frequency regulation, which can further reduce the total cost of energy consumption and make significance for the dispatch of micro-energy-grid