ABSTRACT
Photodynamic therapy (PDT) is one of the new approaches for cancer treatment with high efficacy. However, applications of current photosensitizers are restricted to skin and superficial tumor due to poor in vivo targeting ability, poor water solubility and short wavelength excitement, which limits penetration therefore therapeutic depth. Here, a biodegradable polymeric micelle, methoxy poly(ethylene glycol)-polylactide copolymer (mPEG-PDLLA), is employed as drug delivery system to co-encapsulate strong two-photon absorption compound (LTPA) and photosensitizers. This delivery system is designed to target tumor passively, resulting in near infrared light with an approximately 808 nm wavelength becoming able to indirectly excite photosensitizers through fluorescence resonance energy transfer. Tumor cells and microvessels could be damaged by the generated singlet oxygen. The average size of drug loaded micelles was approximately 55 nm and showed a spherical shape. Both compounds could be released simultaneously from micelles under either weak acid and neutral pH conditions. Reactive oxygen species was produced intracellularly during two-photon PDT process and induced cell apoptosis/necrosis, which was quantified by Annexin-V/FITC assays. Time-dependent ex vivo organ distribution and in vivo anticancer efficacy results suggested that the drug carriers could accumulate in tumors and suppress tumor growth by two-photon PDT. All animals experiments were performed in line with national regulations and approved by the Animal Experiments Ethical Committee of College of Pharmaceutical Sciences, Southwest University. In summary, we have employed two-photon PDT for breast cancer treatment successfully in a mouse model and have demonstrated the significance of delivery system in such therapeutics.
ABSTRACT
Objective: To investigate the modification of live cell membranes with cholesterol linked deoxyribonucleic acid (cholesterol-DNA). Methods: The suspension L1210 cells and adherent PC-12 cells were included. L1210 cells and PC-12 cells were divided into the experimental group (incubated with cholesterol-DNA) and the control group (treated with phosphate buffer saline), respectively. The fluorescence intensity of the cells in the two groups was obtained and the experimental group cells were three-dimensional reconstructed by confocal microscopy. The morphology of the cells in the experimental group was observed by scanning electron microscopy (SEM). The effect of cholesterol-DNA modification on cell membrane fluidity was detected by fluorescence recovery after photobleaching. Results: The results of suspension cells and adherent cells were consistent. Compared with the control group, the fluorescence intensity of cell surface in the experimental group was increased (both P=0.000). Three-dimensional reconstruction of confocal microscopy showed that the fluorescence of the cells in the experimental group was distributed across the surface of the global cell. SEM showed that the morphology of the cells in the experimental group did not change with cholesterol-DNA modification. After fluorescence photobleaching, the relative fluorescence intensity of the L1210 cells in the experimental group was decreased to 0.090, and then recovered to 0.860 within 110 s. Conclusion: Cholesterol-DNA can modify the whole live cell membranes, and the modified cell membranes still have fluidity. This method can modify not only the suspension cells, but also the adherent cells.
ABSTRACT
Objective To describe the genetic epidemiologic features of alopecia areata (AA) patients in China and to presume the possible genetic mo del of AA.Methods A case-controlled study of 1032 AA patients was performed to analyze the effect of genetic factors on the liability to AA.Complex segreg ation and heritability analysis were performed using Falconer's method and SAGE-REGTL programs.Results The mean age of onset was 28.98 ? 13.43 years.The d ifference in the mean age of onset was not significant between males and females.A total of 82.6 percent of patients experienced their first episode of AA befo re the fourth decades of life.A positive family history of AA was obtained in 8 7 patients (8.43%).The prevalences of AA were 1.58%,0.19% and 0.03% in the firs t-,second-and third-degree relatives of the probands respectively,which were significantly higher than those in the controls(P