Dual-sensitive micellar nanoparticles regulate DNA unpacking and enhance gene-delivery efficiency.
Dual-sensitive micellar nanoparticles regulate DNA unpacking and enhance gene-delivery efficiency.
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DOI：
10.1002/adma.200903933
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发表时间：
2010-06-18
影响因子：
29.4
通讯作者：
Mao, Hai-Quan
中科院分区：
文献类型：
--
作者：
Jiang, Xuan;Zheng, Yiran;Chen, Hunter H.;Leong, Kam W.;Wang, Tza-Huei;Mao, Hai-Quan
基于聚合体的基因载体由于其易于合成、转基因大小的灵活性和最小的宿主免疫反应，越来越多地被认为是一种比病毒载体更安全的替代品。然而，在体内应用多阳离子/DNA纳米颗粒的主要挑战是胶体稳定性和血清稳定性差，这分别导致巨噬细胞摄取和纳米颗粒过早解离和DNA有效载荷释放后的快速聚集。它们共同作用，通过静脉注射产生极低的基因传递效率。为了提高效率，理想的多阳离子/DNA递送系统应该满足细胞外环境和内溶酶体腔室的高稳定性要求，使纳米颗粒在循环和内溶酶体隔离中保持其小尺寸和完整性，然后在细胞质和细胞核中保持低稳定性，从而允许DNA释放和转录。最近，我们合成了一系列用于肝脏靶向基因递送的聚乙二醇-聚磷酰胺块(PEG-b-PPA)/DNA胶束纳米颗粒与PPA/DNA纳米颗粒和PEI/DNA复合物相比，PPA/DNA核心周围胶束的PEG电晕有效地减少了蛋白质在生理介质中的吸附，通过尾静脉或胆管输注后改善了血清稳定性，提高了基因在大鼠肝脏中的转染效率。在一系列PEG-b-PPA载波中
Polymer-based gene carriers have been increasingly proposed as a safer alternative to viral vectors, due to their ease of synthesis, flexibility in the size of the transgene to be delivered, and minimal host immune responses. A major challenge to apply polycation/DNA nanoparticles in vivo, however, is the poor colloidal stability and serum stability, which lead to rapid aggregation followed by macrophage uptake, and premature dissociation of nanoparticles and release of DNA payload, respectively. Together they conspire to yield extremely low gene delivery efficiency through intravenous injection. To improve efficiency, an ideal polycation/DNA delivery system should satisfy the conflicting requirements of high stability in extracellular environment and endolysosomal compartments, so that the nanoparticles maintain their small size and integrity in circulation and endosomal sequestration, followed by low stability in cytosol and nucleus so as to allow for DNA release and transcription.Recently, we have synthesized a series of polyethylene glycol-block-polyphosphoramidate (PEG-b-PPA)/DNA micellar nanoparticles for liver-targeted gene delivery.[1] The PEG corona of the micelles around the PPA/DNA core effectively reduced protein adsorption in physiological media and led to improved serum stability and enhanced gene transfection efficiency in the rat liver after infusion through the tail vein or bile duct, as compared with PPA/DNA nanoparticles and PEI/DNA complexes. In a series of PEG-b-PPA carriers
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通过两步QD-Fret对DNA凝结和稳定性的同时非侵入性分析。
影响因子：
17.4
作者：
Chen HH;Ho YP;Jiang X;Mao HQ;Wang TH;Leong KW
通讯作者：
Leong KW
影响因子：
10.8
作者：
Neu, Michael;Germershaus, Oliver;Kissel, Thomas
通讯作者：
Kissel, Thomas
影响因子：
15
作者：
Miyata, K;Kakizawa, Y;Kataoka, K
通讯作者：
Kataoka, K
影响因子：
12.4
作者：
Chen, Hunter H.;Ho, Yi-Ping;Leong, Kam W.
通讯作者：
Leong, Kam W.
影响因子：
4.5
作者：
Manickam, Devika Soundara;Oupicky, David
通讯作者：
Oupicky, David