Polymeric micelles have demonstrated wide utility for chemodrug delivery,which however,still suffer from shortcomings such as undesired drug loading,disassembly upon dilution,pre-leakage of drug cargoes during systemi...Polymeric micelles have demonstrated wide utility for chemodrug delivery,which however,still suffer from shortcomings such as undesired drug loading,disassembly upon dilution,pre-leakage of drug cargoes during systemic circulation,and lack of cancer-selective drug release.Herein,a poly(ethylene glycol)(PEG)-polyphosphoester-based,reactive oxygen species (ROS)-responsive,core-cross-linked (CCL) micellar system was developed to encapsulate both chemodrug (doxorubicin,Dox) and photosensitizer (chlorin e6,Ce6).The hydrophobic core of the micelles was cross-linked via a thioketal (TK)-containing linker,which notably enhanced the drug loading and micelle stability.In tumor cells,far-red light irradiation of Ce6 generated ROS to cleave the TK linkers and disrupt the micelle cores.As such,micelles were destabilized and Dox release was promoted,which thereafter imparted synergistic anti-cancer effect with ROS-mediated photodynamic therapy.This study provides an effective approach to realize the precise control over drug loading,formulation stability,and cancer-selective drug release using polymeric micelles,and would render promising utilities for the programmed anti-cancer combination therapy.展开更多
AIM:To investigate angiopoietin(Ang) and vascular endothelial growth factor(VEGF) expression in rats with ulcerative colitis(UC) and colorectal cancer(CRC).METHODS:Dysplasia and cancer were investigatedin rats that re...AIM:To investigate angiopoietin(Ang) and vascular endothelial growth factor(VEGF) expression in rats with ulcerative colitis(UC) and colorectal cancer(CRC).METHODS:Dysplasia and cancer were investigatedin rats that received three cycles of 3.5% dextran sulfate sodium(DSS) in drinking water for 7 d followed by distilled water for 14 d after intraperitoneal pretreatment with 20 mg/kg 1,2-dimethylhydrazine(DMH)(CRC group).Colitis was investigated in rats that received three cycles of 3.5% DSS in drinking water for 7 d followed by distilled water for 14 d after intraperitoneal pretreatment with saline(UC group).Rats without DSS or DMH treatment served as controls.Expression of the tyrosine kinase with immunoglobulinlike and EGF-like domains(Tie)-2 and its ligands,Ang-1 and Ang-2,as well as VEGF were evaluated in the colorectum by Western blotting.RESULTS:Compared with rats in the control group,rats in the CRC and UC groups developed the symptoms of acute colitis with diarrhea,rectal bleeding,wasting,and loss of body weight(P < 0.05).In addition,the mean length of colorectum of CRC and UC rats was significantly shorter than that of control rats(8.29 ± 0.21 and 8.31 ± 0.86,respectively,vs 12.34 ± 0.12 cm; P < 0.05).Furthermore,rats in the CRC group,but not in the UC or control groups,developed multiple tumors in the colorectal region.Western blot analysis revealed that rats in the CRC and UC groups had markedly increased protein levels of Ang-1,Ang-2,Tie-2,and VEGF in the colorectum compared to rats in the control group.CONCLUSION:Increased expression of Ang-1,Ang-2,Tie-2,and VEGF in ulcerative colitis-derived colorectal cancer might lead to chronic colitis and pathologic angiogenesis in rats.展开更多
文摘Polymeric micelles have demonstrated wide utility for chemodrug delivery,which however,still suffer from shortcomings such as undesired drug loading,disassembly upon dilution,pre-leakage of drug cargoes during systemic circulation,and lack of cancer-selective drug release.Herein,a poly(ethylene glycol)(PEG)-polyphosphoester-based,reactive oxygen species (ROS)-responsive,core-cross-linked (CCL) micellar system was developed to encapsulate both chemodrug (doxorubicin,Dox) and photosensitizer (chlorin e6,Ce6).The hydrophobic core of the micelles was cross-linked via a thioketal (TK)-containing linker,which notably enhanced the drug loading and micelle stability.In tumor cells,far-red light irradiation of Ce6 generated ROS to cleave the TK linkers and disrupt the micelle cores.As such,micelles were destabilized and Dox release was promoted,which thereafter imparted synergistic anti-cancer effect with ROS-mediated photodynamic therapy.This study provides an effective approach to realize the precise control over drug loading,formulation stability,and cancer-selective drug release using polymeric micelles,and would render promising utilities for the programmed anti-cancer combination therapy.
基金Supported by Science and Technology Project of Liaoning Province,No.2013225303the Science and Technology Project of Shenyang City,No.F13-316-1-40
文摘AIM:To investigate angiopoietin(Ang) and vascular endothelial growth factor(VEGF) expression in rats with ulcerative colitis(UC) and colorectal cancer(CRC).METHODS:Dysplasia and cancer were investigatedin rats that received three cycles of 3.5% dextran sulfate sodium(DSS) in drinking water for 7 d followed by distilled water for 14 d after intraperitoneal pretreatment with 20 mg/kg 1,2-dimethylhydrazine(DMH)(CRC group).Colitis was investigated in rats that received three cycles of 3.5% DSS in drinking water for 7 d followed by distilled water for 14 d after intraperitoneal pretreatment with saline(UC group).Rats without DSS or DMH treatment served as controls.Expression of the tyrosine kinase with immunoglobulinlike and EGF-like domains(Tie)-2 and its ligands,Ang-1 and Ang-2,as well as VEGF were evaluated in the colorectum by Western blotting.RESULTS:Compared with rats in the control group,rats in the CRC and UC groups developed the symptoms of acute colitis with diarrhea,rectal bleeding,wasting,and loss of body weight(P < 0.05).In addition,the mean length of colorectum of CRC and UC rats was significantly shorter than that of control rats(8.29 ± 0.21 and 8.31 ± 0.86,respectively,vs 12.34 ± 0.12 cm; P < 0.05).Furthermore,rats in the CRC group,but not in the UC or control groups,developed multiple tumors in the colorectal region.Western blot analysis revealed that rats in the CRC and UC groups had markedly increased protein levels of Ang-1,Ang-2,Tie-2,and VEGF in the colorectum compared to rats in the control group.CONCLUSION:Increased expression of Ang-1,Ang-2,Tie-2,and VEGF in ulcerative colitis-derived colorectal cancer might lead to chronic colitis and pathologic angiogenesis in rats.
