Fe3+-coordinated multifunctional elastic nanoplatform for effective in vivo gene transfection.
Fe3+-coordinated multifunctional elastic nanoplatform for effective in vivo gene transfection.
复制标题
DOI：
10.1021/acsami.9b19585
复制
发表时间：
2020-01
影响因子：
9.5
通讯作者：
Min Zhang;Jeevithan Elango;Xinli Guo;H. Fan;Mingxiao Cui;Mingfu Wang;Kehai Liu
中科院分区：
文献类型：
--
作者：
Min Zhang;Jeevithan Elango;Xinli Guo;H. Fan;Mingxiao Cui;Mingfu Wang;Kehai Liu
非病毒载体在体内转染效率远低于体外转染效率的普遍现象，极大地限制了其进一步的发展和应用。可能的原因是缺乏靶向能力，网状内皮系统（RES）的消除和核转运不足。在这里，一种新的柔性和可变形的聚合物Fe@PEI-R12（tLyp-1-NLS）被报道用于缩短体外和体内基因转染效率之间的差距。通过Fe 3+和低分子量聚乙烯亚胺（LMW-PEI）的配位交联获得的具有变形能力的无定形网络结构Fe@PEI构建了核心并充当基因库，并且当被困在脾脏中时，它可以通过RES过滤孔挤出。双功能肽R12提供了肿瘤靶向和增强的核递送能力。此外，来自Fe@PEI-R12的Fe 3+可以触发内源性过氧化氢（H2 O2）分解以产生O2，从而减少肿瘤缺氧的不利影响。结果表明，Fe@PEI-R12/pDNA复合物可通过膜滤器，循环时间长，且Fe@PEI-R12有在肿瘤组织中蓄积的趋势，并介导pGL 3-Control表达。因此，多功能纳米平台具有有效的体内基因递送的潜力。
The common phenomenon that the non-viral vectors have much lower transfection efficiency in vivo than in vitro greatly restricts its further developments and applications. Possible reasons are lacking targeting ability, elimination by the reticuloendothelial system (RES) and insufficient nuclear transport. Here, a novel flexible and deformable polymer Fe@PEI-R12 (tLyp-1-NLS) is reported for shortening the gap between in vitro and in vivo gene transfection efficiency. The amorphous network structure Fe@PEI with deformation ability acquired by coordination cross-linking of Fe3+ and low molecular weight polyethylenimine (LMW-PEI) constructs the core and serves as the gene reservoir, and it can squeeze out through RES filter holes when trapped in the spleen. The bifunctional peptide R12 provided tumor targeting and enhanced nuclear delivery ability. Additionally, the Fe3+ from Fe@PEI-R12 could trigger endogenous hydrogen peroxide (H2O2) decomposition to produce O2, thereby reducing the adverse effects of tumor hypoxia. It is demonstrated that the Fe@PEI-R12/pDNA complexes could pass through membrane filters, subsequently achieving long circulation time, and Fe@PEI-R12 had a tendency to accumulate in tumor tissue and mediated pGL3-Control expression. Therefore, the multifunctional nanoplatform has the potential for effective in vivo gene delivery.