Peptide-Mediated Tumor Targeting by a Degradable Nano Gene Delivery Vector Based on Pluronic-Modified Polyethylenimine.
Peptide-Mediated Tumor Targeting by a Degradable Nano Gene Delivery Vector Based on Pluronic-Modified Polyethylenimine.
复制标题
基于 Pluronic 修饰的聚乙烯亚胺的可降解纳米基因递送载体进行肽介导的肿瘤靶向
DOI：
10.1186/s11671-016-1337-5
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发表时间：
2016-12
影响因子：
--
通讯作者：
Ding B
中科院分区：
文献类型：
--
作者：
Wu Z;Zhan S;Fan W;Ding X;Wu X;Zhang W;Fu Y;Huang Y;Huang X;Chen R;Li M;Xu N;Zheng Y;Ding B
聚乙烯亚胺（PEI）是一种很有前途的非病毒基因传递载体。为了解决PEI作为基因传递载体的毒效和肿瘤靶向挑战，我们构建了一种新型的非病毒载体dr5 - tat修饰Pluronic-PEI (Pluronic-PEI- dr5 - tat)，该载体是基于低分子量聚乙烯亚胺（lw -PEI）附着在两亲性聚合物Pluronic上，制备Pluronic修饰lw -PEI （Pluronic-PEI）。然后将其与一种多功能肽结合，该肽含有细胞穿透肽（TAT）和一种合成肽，该肽可与癌细胞中过度表达的DR5-a受体结合。该载体降解可控，具有良好的DNA凝聚和保护性能。N/P比为15:1的Pluronic-PEI-DR5-TAT/DNA复合物为122±11.6 nm的球形纳米颗粒，zeta电位约为22±2.8 mV。体外生物学鉴定结果表明，与PEI 25 kDa或Pluronic-PEI形成的复合物相比，Pluronic-PEI-DR5- tat /DNA复合物对DR5受体具有更高的特异性，并且比正常细胞更有效地被肿瘤细胞吸收。因此，与PEI 25 kDa和Pluronic-PEI相比，新型复合物对正常细胞的细胞毒性更低，在肿瘤细胞中的基因转染效率更高。总之，我们的新型、可降解的非病毒肿瘤靶向载体是一种很有希望用于基因治疗的候选载体。
Polyethylenimine (PEI) is considered to be a promising non-viral gene delivery vector. To solve the toxicity versus efficacy and tumor-targeting challenges of PEI used as gene delivery vector, we constructed a novel non-viral vector DR5-TAT-modified Pluronic-PEI (Pluronic-PEI-DR5-TAT), which was based on the attachment of low-molecular-weight polyethylenimine (LMW-PEI) to the amphiphilic polymer Pluronic to prepare Pluronic-modified LMW-PEI (Pluronic-PEI). This was then conjugated to a multifunctional peptide containing a cell-penetrating peptide (TAT) and a synthetic peptide that would bind to DR5—a receptor that is overexpressed in cancer cells. The vector showed controlled degradation, favorable DNA condensation and protection performance. The Pluronic-PEI-DR5-TAT/DNA complexes at an N/P ratio of 15:1 were spherical nanoparticles of 122 ± 11.6 nm and a zeta potential of about 22 ± 2.8 mV. In vitro biological characterization results indicated that Pluronic-PEI-DR5-TAT/DNA complexes had a higher specificity for the DR5 receptor and were taken up more efficiently by tumor cells than normal cells, compared to complexes formed with PEI 25 kDa or Pluronic-PEI. Thus, the novel complexes showed much lower cytotoxicity to normal cells and higher gene transfection efficiency in tumor cells than that exhibited by PEI 25 kDa and Pluronic-PEI. In summary, our novel, degradable non-viral tumor-targeting vector is a promising candidate for use in gene therapy.