Dual-targeting and microenvironment-responsive micelles as a gene delivery system to improve the sensitivity of glioma to radiotherapy

Dbait is a small double-stranded DNA molecule that has been utilized as a radiosensitizer to enhance the sensitivity of glioma to radiotherapy (RT). However, there is no effective drug delivery system to effectively overcome the blood-brain barrier (BBB). The aim of this study was to develop a gene delivery system by using the BBB and glioma dual-targeting and microenvironment-responsive micelles (ch-K(s-s)R8-An) to deliver Dbait into glioma for RT. Angiopep-2 can target the low-density lipoprotein receptor-related protein-1 (LRP1) that is overexpressed on brain capillary endothelial cells (BCECs) and glioma cells. In particular, due to upregulated matrix metalloproteinase 2 (MMP-2) in the tumor microenvironment, we utilized MMP-2-responsive peptides as the enzymatically degradable linkers to conjugate angiopep-2. The results showed that ch-K(s-s)R8-An micelles maintained a reasonable size (80-160 nm) with a moderate distribution and a decreased mean diameter from the cross-linking as well as exhibited low critical micelle concentration (CMC) with positive surface charge, ranging from 15 to 40 mV. The ch-K5(s-s)R8-An/pEGFP showed high gene transfection efficiency , improved uptake in glioma cells and good biocompatibility and . In addition, the combination of ch-K5(s-s)R8-An/Dbait with RT significantly inhibited the growth of U251 cells . Thus, ch-K5(s-s)R8-An/Dbait may prove to be a promising gene delivery system to target glioma and enhance the efficacy of RT on U251 cells.

Individualized lifestyle intervention on the control of metabolic status of type 2 diabetes and evaluation of patient compliance / 中国综合临床

Objective To analyze the effects of individualized lifestyle intervention on compliance and metabolic status of patients with type 2 diabetes mellitus (T2DM).Methods Two hundred T2DM patients were selected and randomly divided into experimental and control groups of 100 patients respectively.The experimental group was given individualized lifestyle intervention for 6 months in addition to conventional oral medications.The intervention was to prescribe diet control and exercise therapy according to the patients' individual conditions.The control group was given conventional treatment and verbal lifestyle intervention for 6 months.Comparison was made in patients compliance and various metabolic markers between the two groups.Results The percentage of conduction of diet control and exercise therapy in experimental group was significantly higher than control group ( Diet control:80 vs.52,x2=7.08,P=0.029;Exercise therapy:78 vs.44,x2=11.207,P=0.004).After intervention,the fasting plasma glucose (FPG),2-hour postprandial blood glucose (2hPG),glycated hemoglobin ( HbA1c),body mass index ( BMI),triglyceride ( TG),total cholesterol (TC),low-density lipoprotein ( LDL-C ),and insulin resistance index ( HOMA-IR ) in experimental group decreased significantly,and high-density lipoprotein ( HDL-C ) increased significantly [FPG:( 8.45 ± 1.46 ) mmol/L vs.(6.66 ± 0.67) mmol/L,P=0.000;2hPG:( 12.76 ± 2.25 ) mmol/L vs.(8.22 ± 1.79) mmol/L,P=0.000;HbA1c:(7.68 ± 1.06 ) ％ vs.( 6.48 ± 0.69 ) ％,P=0.000;BMI:( 25.90 ± 1.72 ) kg/m2 vs.( 22.81 ±1.41 ) kg/m2,P=0.016;TG:(2.57 ±0.68) mmol/Lvs.( 1.88 ±0.35) mmol/L,P=0.006;TC:(5.72 ±0.13) mmol/L vs.(5.14 ± 1.38) mmol/L,P=0.043;LDL-C:(3.28 ±0.10)mmol/L vs.(2.81 ±0.57)mmol/L,P=0.009;HOMA-IR:7.58 ± 0.19 vs.4.58 ± 1.98,P=0.000;HDL-C:( 1.29 ± 0.04) mmol/L vs.( 1.62 ± 0.27 ) mmol/L,P=0.003].The levels of FPG,2hPG,HbA1c,BMI,TG,HOMA-IR also decreased in control group after intervention compared with before intervention [FPG:( 8.67 ± 2.71 ) mmol/L vs.( 7.26 ± 1.21 ) mmol/L,P=0.001;2hPG:( 12.82 ± 2.15 ) mmol/L vs.( 10.85 ± 1.98 ) mmol/L,P=0.000,HbA1c:( 7.75 ± 1.08 ) ％ vs.( 7.01 ± 0.87 ) ％,P=0.002;BMI:( 25.82 ± 1.74 ) kg/m2 vs.( 24.23 ± 1.36 ) kg/m2,P=0.024;TG:(2.47 ±0.75) mmol/L vs.(2.13 ± 0.43 ) mmol/L,P=0.018;HoMA-IR:7.88 ± 0.20 vs.6.15 ± 2.01,P=0.042].No significant difference was found on the values of TC,HDL-C and LDL-C before and after intervention in control group (P ＞ 0.05).The effect of intervention of experimental group was more obvious when compared with control group ( FPG:P=0.036;2hPG:P=0.000;HbA1c:P=0.045;BMI:P=0.037;TG:P=0.022;HoMA-IR:P=0.000).Conclusion Individualized lifestyle intervention can improve the compliance of T2DM patients,and was in favor of control metabolic status of T2DM patients to delay the occurrence and development of complications.