性猛交XXXX乱大交派对,四虎影视WWW在线观看免费 ,137最大但人文艺术摄影,联系附近成熟妇女

作者： Qing Yao†§ , David C. Gutierrez‡, Ngoc Ha Hoang†∥⊥, Dongin Kim†, Ruoning Wang#, Christopher Hobbs*‡, and Lin Zhu*†

† Department of Pharmaceutical Sciences, Irma Lerma Rangel College of Pharmacy, Texas A&M University Health Science Center, Kingsville, Texas 78363, United States

‡ Department of Chemistry, Texas A&M University-Kingsville, Kingsville, Texas 78363, United States

§ Department of Pharmaceutics, College of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016 Liaoning, People’s Republic of China

∥ Nanobiopharmaceutics laboratory, College of Pharmacy, Chung-Ang University, Seoul, South Korea

⊥ Department of Pharmaceutics, Hanoi University of Pharmacy, Ha Noi, Vietnam

# Center for Childhood Cancer and Blood Disease, The Research Institute at Nationwide Children’s Hospital, Ohio State University, Columbus, Ohio 43025-2696, United States

 

摘要：The novel self-assembling bottlebrush polyethylene glycol-polynorbornene-thiocresol block copolymers (PEG-PNB-TC) were synthesized by the ring opening metathesis polymerization (ROMP), followed by functionalization of the polymer backbone via the thio-bromo “click” postpolymerization strategy. The PEG-PNB-TC copolymers could easily self-assemble into the nanoscale core–shell polymeric micelles. The hydrophobic anticancer drugs, such as paclitaxel (PTX), could be loaded into their hydrophobic core to form a stable drug-loaded micelle with a superior drug loading capacity of up to ∼35% (w/w). The sustained drug release behavior of the PEG-PNB-TC micelles was observed under a simulated “sink condition”. Compared with commercial PTX formulation (Taxol), the PTX-loaded PEG-PNB-TC micelles showed the enhanced in vitro cellular uptake and comparable cytotoxicity in the drug-sensitive cancer cells, while the copolymers were much safer than Cremophor EL, the surfactant used in Taxol. Furthermore, curcumin (CUR), a natural chemotherapy drug sensitizer, was successfully coloaded with PTX into the PEG-PNB-TC micelles. High drug loading capacity of the PEG-PNB-TC micelles allowed for easy adjustment of drug doses and the ratio of the coloaded drugs. The combination of PTX and CUR showed synergistic anticancer effect in both the drug mixture and drug coloaded micelles at high CUR/PTX ratio, while low CRU/PTX ratio only exhibited additive effects. The combinatorial effects remarkably circumvented the PTX resistance in the multidrug resistant (MDR) cancer cells. Due to the easy polymerization and functionalization, excellent self-assembly capability, high drug loading capability, and great stability, the PEG-PNB-TC copolymers might be a promising nanomaterial for delivery of the hydrophobic anticancer drugs, especially for combination drug therapy.