位置:成果数据库 > 期刊 > 期刊详情页
生物可裂解树状大分子组装体与智能型基因传递系统
  • ISSN号:1000-3304
  • 期刊名称:《高分子学报》
  • 时间:0
  • 分类:O484.41[理学—固体物理;理学—物理]
  • 作者机构:[1]四川大学国家生物医学材料工程技术研究中心,成都610064, [2]南京工业大学材料科学与工程学院,南京211009
  • 相关基金:国家自然科学基金(基金号51133004,81361140343,51503128); 中德国际合作项目(项目号GZ905); 四川大学优秀青年学者基金(基金号2016SCU04A19)资助项目
中文摘要:

以精氨酸外围功能化、硫辛酸内核功能化的肽类树状大分子为组装基元,在亲疏水作用驱动下形成树状大分子组装体;并通过催化量二硫苏糖醇引发组装体内核的硫辛酸残基交联而获得纳米结构稳定、胞内氧化还原可裂解的智能型基因载体系统.双功能化肽类树状大分子具有精确可控的分子结构;在水溶液中组装、交联后,形成粒径约为72 nm、电位为+30.1 m V的树状大分子组装体.树状大分子组装体能够有效压缩和保护DNA,增强DNA对核酸酶的抵抗力,且具有氧化还原响应性、实现DNA的胞内定点可控释放.树状大分子组装体与DNA复合物(A/P=20)在有血清条件下对HEK 293、Hep G2和Hela 3种细胞系的转染效率均优于阳性对照组PEI(Mw=2.5×10^4,N/P=10,无血清)的转染效果.同时,该树状大分子组装体还具有良好的血清耐受性及生物相容性.

英文摘要:

Development of supramolecular dendritic systems becomes a promising strategy on fabrication of efficient nanoplatforms for therapeutic agent delivery. Arginine-rich and lipoic acid-functionalized peptide dendrons were accurately synthesized using divergent approach and characterized with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Critical aggregation concentration of the amphiphilic peptide dendron was determined to be 209.8 μg/m L using pyrene as fluorescence probe. After supramolecular self-assembly of these peptide dendrons into nanoparticles in water, a catalytic amount of dithiothreitol(DTT) could induce polymerization to generate cross-linked and bio-cleavable dendritic systems(BCDSs) for improving the gene delivery efficiency in normal cells and tumor cells. The size of the disulfide cross-linked dendritic systems became much smaller( ~ 72 nm) than the size of the non-crosslinked dendritic assemblies( ~ 107 nm), which agreed well with the transmission electron microscope results. Agarose gel electrophoresis retardation assay indicated BCDSs completely condensed DNA at an A/P ratio of 5. An appropriate complex size of 80 nm was found at A/P of 20 with uniform spherical nanostructure. The BCDSs/DNA complex could efficiently protect DNA against DNase degradation, while reductive condition(10 mmol/L DTT) could induce the disintegration of nanocomplex and the release of DNA. Then, the confocal laser scan microscopy images indicated that intracellular reductive condition triggered cleavage of disulfide-stabilized supramolecular dendritic system and deliveried DNA into nucleus. Owing to the efficient DNA internalization and redox-responsive release of the BCDSs/DNA complexes(A/P = 20), green fluorescent protein expression was much better than the positive control of PEI group(N/P = 10, in the absence of fetal bovine serum). Quantitative result demonstrated that BCDSs could largely enhance the transfection efficiency of p GL3-Luc by 4.2 times, 2.7 tim

同期刊论文项目
同项目期刊论文
期刊信息
  • 《高分子学报》
  • 中国科技核心期刊
  • 主管单位:中国科学院
  • 主办单位:中国化学会 中国科学院化学研究所
  • 主编:张希
  • 地址:北京市海淀区中关村北一街2号
  • 邮编:100190
  • 邮箱:gfzxb@iccas.ac.cn
  • 电话:010-62588927
  • 国际标准刊号:ISSN:1000-3304
  • 国内统一刊号:ISSN:11-1857/O6
  • 邮发代号:2-498
  • 获奖情况:
  • 国家优秀期刊二等奖,中科院优秀期刊二等奖,中国科协优秀期刊
  • 国内外数据库收录:
  • 俄罗斯文摘杂志,美国化学文摘(网络版),荷兰文摘与引文数据库,美国科学引文索引(扩展库),英国高分子图书馆,日本日本科学技术振兴机构数据库,中国中国科技核心期刊,中国北大核心期刊(2004版),中国北大核心期刊(2008版),中国北大核心期刊(2011版),中国北大核心期刊(2014版),中国北大核心期刊(2000版)
  • 被引量:19174