Structure/function relationships of polyamidoamine/DNA dendrimers as gene delivery vehicles
Structure/function relationships of polyamidoamine/DNA dendrimers as gene delivery vehicles
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DOI：
10.1002/jps.20251
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发表时间：
2005-02-01
影响因子：
3.8
通讯作者：
Middaugh, CR
中科院分区：
文献类型：
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作者：
Braun, CS;Vetro, JA;Middaugh, CR
PAMAM树枝状聚合物是一类多胺聚合物的成员，其表现出显著的基因递送能力。在这项研究中，选择PAMAM树枝状聚合物，跨越一系列的大小（第2，4，7和9代）和转染效率，其特征在于通过各种生物物理方法来搜索与转染相关的结构特性。胶体性质（大小和zeta电位）作为电荷比的函数的测量表明，高度分散的树枝状聚合物/DNA复合物具有4和8之间的大小/zeta电位值。复合物的圆二色性（CD）和FTIR光谱证实了DNA组分。当与高达5：1电荷比（+/-）的所有树枝状聚合物世代结合时保持B形式。等温滴定量热法和差示扫描量热法检测到的变化是相关的聚合物结构和电荷比，但不。与转染效率直接相关。尽管通过CD、FTIR、DSC和ITC检测到的DNA结构和稳定性变化类似于用其他阳离子递送媒介物观察到的那些[例如，阳离子脂质、类肽/类脂质、肽、聚乙烯亚胺（PEI）等]，与转染活性没有明显的相关性。很明显这可能是由于，至少部分是由于复合物的异质性。(C)2004 Wiley-Liss，Inc.和美国药剂师协会
PAMAM dendrimers are members of a class of polyamine polymers that demonstrate significant gene delivery ability. In this study, a selection of PAMAM dendrimers, spanning a range of sizes (generations 2, 4, 7, and 9) and transfection efficiencies, are characterized by various biophysical methods to search for structural properties that correlate with transfection. Measurements of colloidal properties (size and zeta potential) as a function of charge ratio reveal that highly transfecting dendrimer/DNA complexes have size/zeta potential values between 4 and 8. Circular dichroism (CD) and FTIR spectroscopy of complexes confirm the DNA component. remains in B form when associated with all dendrimer generations up to a 5:1 charge ratio (+/-). Isothermal titration calorimetry and differential scanning calorimetry detect changes that are related to polymer structure and charge ratio but do not. directly correlate with transfection efficiency. Despite DNA structural and stability changes detected by CD, FTIR, DSC, and ITC that are similar to those seen with other cationic delivery vehicles [e.g., cationic lipids, peptoids/lipitoids, peptides, polyethyleneimines (PEIs), etc.], clear correlations with transfection activity are not. readily apparent. This may be due, at least in part, to the heterogeneity of the complexes. (C) 2004 Wiley-Liss, Inc. and the American Pharmacists Association.