ABSTRACT
Objective To prepare a thymopentin-contained supramolecular hydrogel, and characterize its micromorphology and mechanical property, and further investigate its effects on the cellular uptake and the immunomodulatory performance in vitro . Methods The self-assembling peptide containing thymopentin was prepared by solid phase synthesis method and identified using LC-MS after being purified by high performance liquid chromatography (HPLC). Supramolecular hydrogel was prepared through a heating-cooling process, and its micromorphology and mechanical property were characterized using transmission electron microscopy (TEM) and rheology. The cellular uptake efficiencies of free thymopentin and thymopentin nanofibers were observed by inverted fluorescence microscope after FITC-labeling. The abilities of free thymopentin and thymopentin nanofibers to stimulate RAW 264.7 cells to secrete tumor necrosis factor (TNF-α) were studied by enzyme-linked immunosorbent assay (ELISA). Results A macroscopic visible supramolecular hydrogel was obtained by a heating-cooling process, composing with long cross-linked nanofibers and possessing good ductility of mechanics. Compared with free thymopentin, thymopentin nanofibers showed much more enhanced cellular uptake, and better immunomodulation property as stimulating the RAW 264.7 cells to produce much higher concentration of TNF-α in vitro . Conclusion After rational structural modification, the cellular uptake and immunomodulatory activity of thymopentin, which formed nanomedicine, were significantly enhanced. This study can provide new methods and guidance for improving the therapeutic effect of thymopentin in clinical application.
ABSTRACT
Objective To design and synthesize a novel type of combined anti-tumor drug-doxorubicin modified silver nanoparticles(DOX-Ag NPs)with pH response,characterize its physical and chemical properties,and investigate its drug responsive release and anti-tumor activity in vitro.Methods DOX-Ag NPs were prepared by coupling silver nanoparticles (Ag NPs) with doxorubicin (DOX) via a LA-NHNH2linker. The structure of LA-NHN=DOX was confirmed by nuclear magnetic resonance(1H NMR)and high resolution mass spectrometry(HRMS).The particle size and micromorphology of the nanoparticles were detected by dynamic light scattering (DLS) and transmission electron microscopy (TEM), respectively. The optical properties of the nanoparticles were characterized by UV-vis absorption spectroscopy and fluorescence spectroscopy.The DOX release kinetics of DOX-Ag NPs under different pH conditions were examined by dialysis method combined with fluorescence spectroscopy. The in vitro anti-tumor effects of DOX-Ag NPs were evaluated by MTT assay. Results DOX-Ag NPs were spherical nanoparticles with a particle size of (40.4 ± 3.8) nm. DOX-Ag NPs could rapidly release DOX under weak acid condition.DOX-Ag NPs significantly inhibited the proliferation and cell viability of HepG2 cells in concentration dependent manner.When DOX concentration was 0.5-20 mg/L(Ag concentration was 0.45-18 mg/L), the cell survival rate was significantly lower in DOX-Ag NPs group than that of DOX group and Ag NPs group(P<0.05). Conclusion DOX-Ag NPs are a combined anti-tumor nano-drug with pH-responsive ability, which can release DOX rapidly in tumor tissues and play an anti-tumor effect through synergistic treatment with Ag NPs in vitro.