E838对放射损伤小鼠活存及造血功能的影响

动物照射前后不同时间给予新型抗放药E838腹腔注射 ,观察其死亡率和死亡动物活存时间 ,并在用药后不同时间检测其外周血白细胞数、骨髓有核细胞数、骨髓粒系祖细胞集落形成单位CFU -GM和造血干细胞CFU -S数 ,研究了E838对放射损伤小鼠存活及造血功能的影响。结果表明 ,E838预防用药能够明显提高损伤动物的 30d存活率及平均活存时间 ,对造血功能的研究结果也表明 ,E838预防用药能够减少损伤后外周血白细胞数、骨髓有核细胞数、骨髓粒 -单系祖细胞数及造血干细胞CFU -S数的下降幅度。显示出E838对放射损伤具有确切的预防效果 。

Antioxidant therapy for chronic hepatitis C after failure of interferon:Results of phase Ⅱ randomized,double-blind placebo controlled clinical trial

AIM： TO assess the safety and efficacy of antioxidant therapy for patients with chronic hepatitis C virus （HCV） infection.METHODS： One hundred chronic HCV infection patients failed in interferon treatment were enrolled and randomly assigned to receive combined intravenous and oral antioxidants or placebo, or oral treatment alone, Primary end points were liver enzymes, HCV-RNA levels and histology.RESULTS： Combined oral and intravenous antioxidant therapy was associated with a significant decline in ALT levels in 52% of patients who received antioxidant therapy vs 20% of patients who received placebo （P = 0.05）. Histology activity index （HAI） score at the end of treatment was reduced in 48% of patients who received antioxidant therapy vs 26% of patients who received placebo （P = 0.21）. HCV-RNA levels decreased by l-log or more in 28% of patients who received antioxidant therapy vs 12% who received placebo （P = NS）. In part 11 of the trial, oral administration of antioxidants was not associated with significant alterations in any of the end points.CONCLUSION： Antioxidant therapy has a mild beneficial effect on the inflammatory response of chronic HCV infection patients who are non-responders to interferon. Combined antiviral and antioxidant therapy may be beneficial for these patients.

Studies on In Vitro Slow-Release Characteristics and Anticancer Effect of 5-Fluorouracil-Loaded Immuno-Nanoparticles

OBJECTIVE To investigate slow-release features of biodegradable anticancer 5-fluorouracil-loaded immunonanoparticles （5-FU INPs）, and to assess their tumor cell killing activity in vitro.METHODS The method of vibrating dialysis at a constant temperature, and first-order derivative ultraviolet spectrophotometry were used to determine the drug-releasing character of 5-FU INPs. The methyl thiazolyl tetrazolium （MTT） colorimetric method was employed to assay the killing activity of 5-FU INPs on 5 tumor cell lines at different phases.RESULTS The 5-FU INPs had a favorable slow-release function, with a tl/2 release time of 10.4 days. The 5-FU INPs had a rather strong lethal effect on 5 tumor cell lines resulting in a positive correlativity between the killing activity and the action time and amount of the drug released.CON＇CLUSION The drug disposition is uniform from the 5-FU INPs, and there is no impact on efficacy of the 5-FU during preparation and degradation of the 5-FU INPs. The 5-FU INPs have a favorable function for drug release, and can maintain an effective killing activity over a long period of time.

Smart Nanomedicine for Ondemand Drug Release and Synergistic Antitumor Therapy

Smart nanoparticles（NPs）that respond to external and internal stimulations have been developing to achieve optimal drug release in tumor.However,applying these smart NPs to attain high antitumor performance is hampered by limited drug carriers and inefficient spatiotemporal control.Recently,a research team led by CAI Lintao from the Institute of Biomedicine and Biotechnology,

Polypeptide dendrimers: Self-assembly and drug delivery

Amphiphilic dendritic poly（glutarnic acid）-b-polyphenylalanine copolymers were synthesized using generation 3 dendritic poly（glutamic acid） as the macroinitiator in the ring-opening polymerization of NCA-Phe. The block copolymers self-assembled micelles with polyphenylalanine segments as core and dendritic poly（glutamic acid） segments as shell. The biocompatibility of the micelles was studied. The release of the anticancer drug doxorubicin from the micelles was investigated in vitro. The results showed that the sustaining release of the drug could last for 60 h. The micellar drug release system was efficient in inhibiting the proliferation of HepG2 liver cancer cells, 75% cancer cells were killed under appropriate in vitro incubation.

Self-assembled multifunctional DNA nanoflowers for the circumvention of multidrug resistance in targeted anticancer drug delivery

Cancer chemotherapy has been limited by its side effects and multidrug resistance （MDR）, the latter of which is partially caused by drug efflux from cancer cells. Thus, targeted drug delivery systems that can circumvent MDR are needed. Here, we report multifunctional DNA nanoflowers （NFs） for targeted drug delivery to both chemosensitive and MDR cancer cells that circumvented MDR in both leukemia and breast cancer cell models. NFs are self-assembled via potential co-precipitation of DNA and magnesium pyrophosphate generated by rolling circle replication, during which NFs are incorporated using aptamers for specific cancer cell recognition, fluorophores for bioimaging, and doxorubicin （Dox）- binding DNA for drug delivery. NF sizes are tunable （down to N200 nm in diameter）, and the densely packed drug-binding motifs and porous intrastructures endow NFs with a high drug-loading capacity （71.4%, wt/wt）. Although the Dox- loaded NFs （NF-Dox） are stable at physiological pH, drug release is facilitated under acidic or basic conditions. NFs deliver Dox into target chemosensitive and MDR cancer cells, preventing drug efflux and enhancing drug retention in MDR cells. NF-Dox induces potent cytotoxicity in both target chemosensitive cells and MDR cells, but not in nontarget cells, thus concurrently circumventing MDR and reducing side effects. Overall, these NFs are promising tools for circumventing MDR in targeted cancer therapy.