High-density lipoproteins(HDL) are naturally-occurring nanoparticles that are biocompatible,non-immunogenic and completely biodegradable. These endogenous particles can circulate for an extended period of time and tra...High-density lipoproteins(HDL) are naturally-occurring nanoparticles that are biocompatible,non-immunogenic and completely biodegradable. These endogenous particles can circulate for an extended period of time and transport lipids, proteins and micro RNA from donor cells to recipient cells.Based on their intrinsic targeting properties, HDL are regarded as promising drug delivery systems. In order to produce on a large scale and to avoid blood borne pollution, reconstituted high-density lipoproteins(rHDL) possessing the biological properties of HDL have been developed. This review summarizes the biological properties and biomedical applications of rHDL as drug delivery platforms. It focuses on the emerging approaches that have been developed for the generation of biomimetic nanoparticles rHDL to overcome the biological barriers to drug delivery, aiming to provide an alternative,promising avenue for efficient targeting transport of nanomedicine.展开更多
Accumulation of extracellular β-amyloid （Aβ） is crucial for the pathogenesis of Alzheimer＇s disease （AD）, and the development of novel therapeutic agents that can both accelerate Aβ clearance and inhibit the s...Accumulation of extracellular β-amyloid （Aβ） is crucial for the pathogenesis of Alzheimer＇s disease （AD）, and the development of novel therapeutic agents that can both accelerate Aβ clearance and inhibit the subsequent pathological cascades is regarded as a promising strategy for AD management. In our previous study, we have constructed discoidal apolipoprotein E3-reconstituted high-density lipoprotein （ApoE3-rHDL） as an efficient nanoplatform that can penetrate the blood-brain barrier and accelerate Aβ clearance for a combination treatment of AD. To further improve its drug loading capacity, we hypothesized that spherical rHDL might serve as a more powerful nanocarrier if it has the same brain delivery and Aβ clearance abilities as the discoidal rHDL does. To evaluate the potential of spherical rHDL as a promising alternative for the combination therapy for AD, here, we investigated the effect of the shape of rHDL on its brain delivery, Aβ clearance, and anti-AD efficacy. We found that spherical rHDL had stronger Aβ-binding affinity than discoidal rHDL did, more effectively facilitated microglial uptake and degradation of Aβ-42, achieved better brain distribution after intravenous administration, and more powerfully reduced Aβ deposition, decreased microglia activation, attenuated neurological damage, and rescued memory deficits in a mouse model of AD. Among the rHDLs evaluated, monosialotetrahexosyl ganglioside-incorporated spherical rHDL exerted the best effect. The findings of this study for the first time show a shape effect of an rHDL nanocarrier on its biological functions and suggest that a spherical lipoprotein-mimic nanocarrier may serve as a more efficient multifunctional nanoplatforrn for AD therapy.展开更多
目的:研究具有肿瘤多药耐药逆转活性的四氢异喹啉类化合物HZ08-重组高密度脂蛋白(reconsdtuted high density lipoprotein,rHDL)纳米粒的构建及性质,旨在研制HZ08的新型仿生纳米制剂。方法:通过胆酸钠法制备HZ08-rHDL纳米粒,考察该纳米...目的:研究具有肿瘤多药耐药逆转活性的四氢异喹啉类化合物HZ08-重组高密度脂蛋白(reconsdtuted high density lipoprotein,rHDL)纳米粒的构建及性质,旨在研制HZ08的新型仿生纳米制剂。方法:通过胆酸钠法制备HZ08-rHDL纳米粒,考察该纳米粒的包封率、载药量、渗漏率、形态、粒径等理化性质,透析法研究制剂的体外释放特性,MTT法考察rHDL载体对人乳腺癌细胞(MCF-7)和人正常乳腺细胞(MCF-10A)的毒性。HPLC法、流式细胞术和荧光显微术评价纳米粒的肿瘤细胞靶向性。结果:HZ08-rHDL纳米粒包封率(93.45±0.28)%,载药量(10.65±0.46)%,水分散液于4℃放置一个月渗漏率为(4.50±0.12)%,外观呈圆整球形,平均粒径为(105.53±2.50)nm;体外48 h累积释放量仅为(12.13±1.08)%;rHDL载体细胞毒性低,且MCF-7细胞对rHDL荷栽药物的摄取能力显著强于MCF-10A细胞(P<0.0001),有较强的体外肿瘤靶向性。结论:HZ08-rHDL纳米粒的包封率高、性质稳定、粒径大小适宜、缓释效果明显、载体毒性低且有较好的肿瘤细胞靶向性,具有继续研究开发的价值。展开更多
目的:建立一种重组高密度脂蛋白(reconstituted high density lipoprotein,rHDL)载p53基因纳米粒的制备方法。方法:采用阳离子脂质材料包裹、压缩p53基因,形成复合物,考察其粒径、电位、体外稳定性;薄膜分散法制备rHDL载基因纳米粒,并研...目的:建立一种重组高密度脂蛋白(reconstituted high density lipoprotein,rHDL)载p53基因纳米粒的制备方法。方法:采用阳离子脂质材料包裹、压缩p53基因,形成复合物,考察其粒径、电位、体外稳定性;薄膜分散法制备rHDL载基因纳米粒,并研究rHDL载基因纳米粒的粒径、电位、形态、包封率和血清稳定性。结果:选用双十八烷基二甲基溴化铵(dimethyldioctadecylammonium bromide,DODAB)压缩p53基因形成DODAB/p53复合物;在最优N/P比时,该复合物粒径为(102.0±0.7)nm,电位为(10.50±0.75)mV,复合物仅在高浓度肝素条件下出现解聚,且其血清稳定性良好。rHDL能有效包载上述复合物形成rHDL载基因纳米粒,该纳米粒粒径为(104.3±5.8)nm,电位为(-10.70±3.24)mV,外观呈球形结构,p53基因包封率为78.09%,且血清稳定性良好。结论:成功制备了rHDL载p53基因纳米粒,且该纳米粒具有良好的理化性质及体外稳定性,为其后期体内外抗肿瘤作用的研究打下了实验基础。展开更多
基金supported by National Natural Science Foundation of China (Nos. 81373351, 81573382, and 81722043)grant from Shanghai Science and Technology Committee (15540723700)"Shu Guang" project supported by Shanghai Municipal Education Commission and Shanghai Education Development Foundation (15SG14)
文摘High-density lipoproteins(HDL) are naturally-occurring nanoparticles that are biocompatible,non-immunogenic and completely biodegradable. These endogenous particles can circulate for an extended period of time and transport lipids, proteins and micro RNA from donor cells to recipient cells.Based on their intrinsic targeting properties, HDL are regarded as promising drug delivery systems. In order to produce on a large scale and to avoid blood borne pollution, reconstituted high-density lipoproteins(rHDL) possessing the biological properties of HDL have been developed. This review summarizes the biological properties and biomedical applications of rHDL as drug delivery platforms. It focuses on the emerging approaches that have been developed for the generation of biomimetic nanoparticles rHDL to overcome the biological barriers to drug delivery, aiming to provide an alternative,promising avenue for efficient targeting transport of nanomedicine.
基金This work was supported by the National Natural Science Foundation of China （Nos. 81373351, 81573382, 81722043, and 81503174）, the National Science and Technology Major Project （No. 2018ZX09734005-007）, the National Youth Talent Support Program, grant from Shanghai Science and Technology Committee （No. 15540723700）, and ＂Shu Guang＂ project supported by Shanghai Municipal Education Commission and Shanghai Education Development Foundation （No. 15SG14）.
文摘Accumulation of extracellular β-amyloid （Aβ） is crucial for the pathogenesis of Alzheimer＇s disease （AD）, and the development of novel therapeutic agents that can both accelerate Aβ clearance and inhibit the subsequent pathological cascades is regarded as a promising strategy for AD management. In our previous study, we have constructed discoidal apolipoprotein E3-reconstituted high-density lipoprotein （ApoE3-rHDL） as an efficient nanoplatform that can penetrate the blood-brain barrier and accelerate Aβ clearance for a combination treatment of AD. To further improve its drug loading capacity, we hypothesized that spherical rHDL might serve as a more powerful nanocarrier if it has the same brain delivery and Aβ clearance abilities as the discoidal rHDL does. To evaluate the potential of spherical rHDL as a promising alternative for the combination therapy for AD, here, we investigated the effect of the shape of rHDL on its brain delivery, Aβ clearance, and anti-AD efficacy. We found that spherical rHDL had stronger Aβ-binding affinity than discoidal rHDL did, more effectively facilitated microglial uptake and degradation of Aβ-42, achieved better brain distribution after intravenous administration, and more powerfully reduced Aβ deposition, decreased microglia activation, attenuated neurological damage, and rescued memory deficits in a mouse model of AD. Among the rHDLs evaluated, monosialotetrahexosyl ganglioside-incorporated spherical rHDL exerted the best effect. The findings of this study for the first time show a shape effect of an rHDL nanocarrier on its biological functions and suggest that a spherical lipoprotein-mimic nanocarrier may serve as a more efficient multifunctional nanoplatforrn for AD therapy.
文摘目的:研究具有肿瘤多药耐药逆转活性的四氢异喹啉类化合物HZ08-重组高密度脂蛋白(reconsdtuted high density lipoprotein,rHDL)纳米粒的构建及性质,旨在研制HZ08的新型仿生纳米制剂。方法:通过胆酸钠法制备HZ08-rHDL纳米粒,考察该纳米粒的包封率、载药量、渗漏率、形态、粒径等理化性质,透析法研究制剂的体外释放特性,MTT法考察rHDL载体对人乳腺癌细胞(MCF-7)和人正常乳腺细胞(MCF-10A)的毒性。HPLC法、流式细胞术和荧光显微术评价纳米粒的肿瘤细胞靶向性。结果:HZ08-rHDL纳米粒包封率(93.45±0.28)%,载药量(10.65±0.46)%,水分散液于4℃放置一个月渗漏率为(4.50±0.12)%,外观呈圆整球形,平均粒径为(105.53±2.50)nm;体外48 h累积释放量仅为(12.13±1.08)%;rHDL载体细胞毒性低,且MCF-7细胞对rHDL荷栽药物的摄取能力显著强于MCF-10A细胞(P<0.0001),有较强的体外肿瘤靶向性。结论:HZ08-rHDL纳米粒的包封率高、性质稳定、粒径大小适宜、缓释效果明显、载体毒性低且有较好的肿瘤细胞靶向性,具有继续研究开发的价值。
文摘目的:建立一种重组高密度脂蛋白(reconstituted high density lipoprotein,rHDL)载p53基因纳米粒的制备方法。方法:采用阳离子脂质材料包裹、压缩p53基因,形成复合物,考察其粒径、电位、体外稳定性;薄膜分散法制备rHDL载基因纳米粒,并研究rHDL载基因纳米粒的粒径、电位、形态、包封率和血清稳定性。结果:选用双十八烷基二甲基溴化铵(dimethyldioctadecylammonium bromide,DODAB)压缩p53基因形成DODAB/p53复合物;在最优N/P比时,该复合物粒径为(102.0±0.7)nm,电位为(10.50±0.75)mV,复合物仅在高浓度肝素条件下出现解聚,且其血清稳定性良好。rHDL能有效包载上述复合物形成rHDL载基因纳米粒,该纳米粒粒径为(104.3±5.8)nm,电位为(-10.70±3.24)mV,外观呈球形结构,p53基因包封率为78.09%,且血清稳定性良好。结论:成功制备了rHDL载p53基因纳米粒,且该纳米粒具有良好的理化性质及体外稳定性,为其后期体内外抗肿瘤作用的研究打下了实验基础。
