ABSTRACT
Objective To design and synthesize a novel paclitaxel loaded nanoparticle with reactive oxygen species (ROS) response, and characterize its structure, and investigate its stability, in vitro drug responsive release, cellular uptake and in vitro antitumor activity. Methods The PEG-2S-PTX monomer was synthesized by coupling the hydrophilic polyethylene glycol (PEG) with hydrophobic paclitaxel (PTX) via a thioether chain (2S), and the prodrug nanoparticles (PEG-2S-PTX NPs) were prepared by self-assembly. Meanwhile, using succinic anhydride (SA) as the linking group to synthesize the PEG-SA-PTX monomer and prepare the other prodrug nanoparticles (PEG-SA-PTX NPs) as control. The structures of PEG-2S-PTX and PEG-SA-PTX monomer were confirmed by 1H-NMR. The diameter and stability of the nanoparticles were detected by dynamic light scattering (DLS). The PTX release kinetics under oxidizing condition was detected by high performance liquid chromatography (HPLC) method. And the cellular uptake efficiency of nanoparticles by MCF-7 cells was observed by fluorescence microscope. The in vitro antitumor effects of nanoparticles were compared by MTT assay. Results PEG-2S-PTX and PEG-SA-PTX could both be self-assemble into nanoparticles with the diameter of (92.15±12.42) nm and (113.20±12.16) nm. PEG-2S-PTX NPs could rapidly release PTX under oxidative condition while PEG-SA-PTX NPs only showed weak responsiveness. PEG-2S-PTX NPs could be more rapidly taken up by MCF-7 cells compared with PEG-SA-PTX NPs. They both showed concentration dependent anti-tumor effects, but the cytotoxicity of PEG-2S-PTX NPs was stronger than that of PEG-SA-PTX NPs in the concentrations of 0.05, 0.1, 5, 10, 50 and 100 mg/L (P<0.05). Conclusion As paclitaxel prodrug nanoparticles with ROS responsive ability, PEG-2S-PTX NPs can rapidly release PTX in response to ROS in tumor cells, and exhibit great anti-tumor activity in vitro.
ABSTRACT
Radiotherapy is one of the most important methods to treat malignant tumors. Due to the presence of radiation resistance, the effect of radiotherapy is not entirely satisfactory. To alleviate radiation resistance and improve the radiotherapy effect, radiosensitizers have emerged. As a newly discovered radiosensitizer, RRx-001 has a good clinical application prospect. This paper reviewed the research progress of RRx-001 in source, safety, radiotherapy sensitizing activity and related mechanisms.
ABSTRACT
Objective To synthesize a new kind of acid-sensitive doxorubicin prodrug nanoparticles and to evaluate its anti-brain glioma effect and efficiency through blood-brain barrier (BBB). Methods The prodrug acid-sensitive poly-ethylene glycol (PEG)-doxorubicin (PEG-DOX) copolymer was synthesized by Schiff base reaction, and PEG-DOX pro-drug nanoparticles (PEG-DOX NPs) were prepared by self-assembling. The character of PEG-DOX copolymer was detected by dynamic light scattering (DLS) instrument and 1H NMR. The morphology of PEG-DOX NPs was observed by transmission electron microscopy (TEM). The character of drug release was detected by UV mothed. The cellular uptake efficiency of glio-ma cells to PEG-DOX NPs was observed by inverted fluorescence microscope. The anti-brain glioma effects of PEG-DOX NPs and Free DOX were studied by MTT mothed. PS80-PEG-DOX NPs were gained by the modification of PEG-DOX NPs with Tween 80. Nine BALB/c mice were separated into Free DOX, PEG-DOX NPs and PS80-PEG-DOX NPs groups by ran-dom drawing lots. The mean fluorescence intensity of brain and main organs were observed by in vivo imaging system. Re-sults The copolymer of PEG-DOX can self-assemble into nanoparticles with the diameter of 100 nm. PEG-DOX NPs can quickly release DOX in acid environment. Although PEG-DOX NPs had slow cancer cell uptake than Free DOX, it had lon-ger accumulation. MTT results showed that PEG-DOX NPs had concentration dependent anti-brain glioma effect. Indepen-dent samples t-test indicated that the efficiency through BBB was significantly higher in PS80-PEG-DOX NPs group than that of Free DOX group and PEG-DOX NPs group. Conclusion PEG-DOX NPs show well anti-brain glioma effect in vi-tro, and can across BBB with high efficiency after modification, which make it possible for a potential therapeutic prodrug for brain glioma.
ABSTRACT
Objective To compare the biodistribution difference of peptide nanofibers, which were self-assembled by peptide composed of L-or D-amino acids, respectively, and provide the guidance for the in vivo applications of peptide nanofibers. Methods The Nap-GFFYGRGD (L-peptide) and Nap-GDFDFDYGRGD (D-peptide, F and Y were D-configura-tion) were synthesized with solid phase peptide synthesis (SPPS). The structure of the two peptides was identified by nuclear magnetic resonance spectroscopy (1H NMR) and high-resolution mass spectrometry (HR-MS). The two peptides could self-assemble into nanofibers during the cooling process after being boiled. The morphology of the nanofibers was observed with transmission electron microscope (TEM). The peptides were radiolabeled with iodine-125 and self-assembled into nanofi-bers, which were then administered into BALB/c mice via tail vein. The blood samples were collected and then mice were sacrificed at 1, 3, 6 and 12 hours. The main organs (heart, liver, spleen, lung, kidney, stomach, large intestine, small intes-tine, muscle and brain) were isolated and weighed. The radioactivity of organs was detected with a gamma counter. Results The two peptides could self-assemble into nanofibers with diameter of 10-20 nanometers. There were no significant differ-ences in the diameter and morphology between two naofibers. There was significant difference in the biodistribution between two nanofibers. The blood concentration of D-fiber was (8.17±0.32)%ID/g at one hour after injection and then cleared rapid-ly from the blood. The blood concentration of L-fiber was (5.96±0.30)%ID/g at one hour after injection and maintained at a stable level for six hours. The L-fiber was mainly distributed in stomach while the D-fiber was mainly accumulated in liver. Conclusion The configuration of amino acids (D/L) could affect the biodistribution of peptide nanofibers dramatically, which may provide the guidance for the medical applications of peptide nanofibers.
ABSTRACT
Objective To explore the application value of dipstick dye immuno-assay (DDIA) for screening the schistosomiasis chemotherapy targets in the low endemic areas of Xiaogan City.Methods The residents aged 6-65 years in a village in the low endemic areas of schistosomiasis of Xiaogan City were selected and tested by the methods of fecal examination,DDIA,indirect hemagghitination (IHA),enzyme linked immunosorbent assay (ELISA) and inquiry,and the results of fecal examination were determined as the gold standard.Results The Youden' s indices of IHA,DDIA,ELISA and inquiry were 0.74,0.72,0.62 and 0.30,respectively,and the consistency rates of them were 93.38%,91.99%,81.53% and 70.03%,respectively.It took 16.70,4.95,4.12,5.63 and 2.44 Yuan screening one patient with the fecal examination,IHA,DDIA,ELISA and inquiry,respectively.Conclusion The validity of DDIA with simple operation and low cost for screening the schistosomiasis chemotherapy targets is satisfying,and the method is suitable for large scale screening in low endemic areas.