OBJECTIVE To review the application of nanoparticles modified with angiopep-2,providing theoretical guidance for the diagnosis and treatment of glioma. METHODS According to domestic and foreign research reports of nan...OBJECTIVE To review the application of nanoparticles modified with angiopep-2,providing theoretical guidance for the diagnosis and treatment of glioma. METHODS According to domestic and foreign research reports of nanoparticles modified with angiopep-2 in recent years,the application in the diagnosis and treatment of glioma was summarized and analyzed. RESULTS Angiopep-2 can be modified to the surface of nanoparticles loaded with imaging agents or chemotherapeutic agents,which can significantly improve the imaging effect of glioma and achieve targeted drug delivery. CONCLUSION Angiopep-2 exhibits a high brain penetration capability in blood brain barrier and in glioma cells. The nanoparticles modified with angiopep-2 can delivery various imaging agents and chemotherapeutic agents to glioma cells,the dual-targeting delivery systems can provide theoretical guidance for the diagnosis and treatment of glioma.展开更多
OBJECTIVE The greatest challenge in chemotherapy of ischemic stroke is the construction a suitable delivery system to overcome the poor physicochemical properties of drug and its low permeability across the blood brai...OBJECTIVE The greatest challenge in chemotherapy of ischemic stroke is the construction a suitable delivery system to overcome the poor physicochemical properties of drug and its low permeability across the blood brain barrier(BBB).METHODS In the present study,dendrimer,polyamidoamine(PAMAM),was synthesized as the nano-drug carriers.Angiopep-2,which has been proved excellent ability to cross the BBB,was exploited as the targeting ligand to conjugate PAMAM via bifunctional polyethylene glycol(PEG).Then scutellarin(STA)was encapsulated into the functionalized nanoparticles(NPs)to formulate Angiopep-2 modified STA-loaded PEG-PAMAM NPs.Ischemic stroke model was established to evaluate the treatment efficacy and protective mechanism of Angiopep-2-STA-PEG-PAMAM NPs.RESULTS The pharmacokinetics and biodistribu-tion demonstrated that Angiopep-2-STA-PEG-PAMAM NPs exhibited significantly higher plasma concentration from 1 h to 10 h after intravenous administration and improve accumulation in brain(4.7-fold)compared with STA solution.Moreover,prolonged elimination half-life(4.8-fold)and lower clearance(3.4-fold)were observed.The brain uptake study of 6-coumarin confirmed that Angiopep-2-PEG-PAMAM NPs possessed better brain targeting efficacy(3.2-fold)than PEG-PAMAM NPs.Angiopep-2-STA-PEG-PAMAM NPs obviously ameliorated infarct volume,neurological deficit,histopathological severity and neuronal apoptosis.In addition,Angiopep-2-STA-PEG-PAMAM NPs markedly inhibited the calcium content and the levels of IL-12p40,IL-13,IL-17 and IL-23.Furthermore,Angiopep-2-STA-PEG-PAMAM NPs significantly decreased the m RNA and protein expressions of HMGB1,TLR2,TLR4,TLR5,My D88,TRIF,TRAM,IRAK-4,TRAF6,IкBα,IKKβand NF-кBp65.CONCLUSION The results suggested that Angiopep-2modified scutellarin-loaded PEG-PAMAM nanocarriers possessed remarkable neuroprotective effects on ischemic stroke through modulation of inflammatory cascades and HMGB1/TLRs/MyD 88-induced NF-κB activation pathways.展开更多
文摘脑胶质瘤是常见的原发性颅内肿瘤,其难以治愈的主要原因为血脑脊液屏障(blood-cerebrospinal fluid barrier,blood-CSF barrier)的存在阻碍了化疗药物进入脑内,大大降低了有效药物浓度。此外,肉眼可见的肿瘤已经处于中后期,失去了最佳的治疗时机。Angiopep-2为低密度脂蛋白受体相关蛋白(low density lipoprotein receptor related protein,LRP)的配体,血脑脊液屏障和胶质瘤细胞表面都高度表达LRP受体。Angiopep-2具有靶向性,将其修饰到装载化疗药物和显像剂的纳米粒子表面,可以实现靶向释药,提高胶质瘤成像效果。该文综述了以Angiopep-2修饰的装载不同药物的纳米系统在胶质瘤中的应用,为胶质瘤的诊断和治疗提供了思路和方法。
文摘OBJECTIVE To review the application of nanoparticles modified with angiopep-2,providing theoretical guidance for the diagnosis and treatment of glioma. METHODS According to domestic and foreign research reports of nanoparticles modified with angiopep-2 in recent years,the application in the diagnosis and treatment of glioma was summarized and analyzed. RESULTS Angiopep-2 can be modified to the surface of nanoparticles loaded with imaging agents or chemotherapeutic agents,which can significantly improve the imaging effect of glioma and achieve targeted drug delivery. CONCLUSION Angiopep-2 exhibits a high brain penetration capability in blood brain barrier and in glioma cells. The nanoparticles modified with angiopep-2 can delivery various imaging agents and chemotherapeutic agents to glioma cells,the dual-targeting delivery systems can provide theoretical guidance for the diagnosis and treatment of glioma.
基金The project supported by National Natural Science Foundation of China(NSFC 21476054)the Natural Science Foundation of Heilongjiang Province(B201407)
文摘OBJECTIVE The greatest challenge in chemotherapy of ischemic stroke is the construction a suitable delivery system to overcome the poor physicochemical properties of drug and its low permeability across the blood brain barrier(BBB).METHODS In the present study,dendrimer,polyamidoamine(PAMAM),was synthesized as the nano-drug carriers.Angiopep-2,which has been proved excellent ability to cross the BBB,was exploited as the targeting ligand to conjugate PAMAM via bifunctional polyethylene glycol(PEG).Then scutellarin(STA)was encapsulated into the functionalized nanoparticles(NPs)to formulate Angiopep-2 modified STA-loaded PEG-PAMAM NPs.Ischemic stroke model was established to evaluate the treatment efficacy and protective mechanism of Angiopep-2-STA-PEG-PAMAM NPs.RESULTS The pharmacokinetics and biodistribu-tion demonstrated that Angiopep-2-STA-PEG-PAMAM NPs exhibited significantly higher plasma concentration from 1 h to 10 h after intravenous administration and improve accumulation in brain(4.7-fold)compared with STA solution.Moreover,prolonged elimination half-life(4.8-fold)and lower clearance(3.4-fold)were observed.The brain uptake study of 6-coumarin confirmed that Angiopep-2-PEG-PAMAM NPs possessed better brain targeting efficacy(3.2-fold)than PEG-PAMAM NPs.Angiopep-2-STA-PEG-PAMAM NPs obviously ameliorated infarct volume,neurological deficit,histopathological severity and neuronal apoptosis.In addition,Angiopep-2-STA-PEG-PAMAM NPs markedly inhibited the calcium content and the levels of IL-12p40,IL-13,IL-17 and IL-23.Furthermore,Angiopep-2-STA-PEG-PAMAM NPs significantly decreased the m RNA and protein expressions of HMGB1,TLR2,TLR4,TLR5,My D88,TRIF,TRAM,IRAK-4,TRAF6,IкBα,IKKβand NF-кBp65.CONCLUSION The results suggested that Angiopep-2modified scutellarin-loaded PEG-PAMAM nanocarriers possessed remarkable neuroprotective effects on ischemic stroke through modulation of inflammatory cascades and HMGB1/TLRs/MyD 88-induced NF-κB activation pathways.