Host-Guest Interaction-Based Dual response core/shell nanoparticles as efficient siRNA carrier for killing breast cancer cells
Host-Guest Interaction-Based Dual response core/shell nanoparticles as efficient siRNA carrier for killing breast cancer cells
复制标题
基于主客体相互作用的双响应核/壳纳米颗粒作为有效的 siRNA 载体杀死乳腺癌细胞
DOI：
10.1016/j.colsurfb.2021.111918
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发表时间：
2021
影响因子：
5.8
通讯作者：
Xue Wei
中科院分区：
文献类型：
--
作者：
Liang Jinglan;Wu Chengguang;Zhou Xiaoyan;Shi Yunfeng;Xu Jun;Cai Xiang;Fu Tingling;Ma Dong;Xue Wei
如何克服多重障碍，实现治疗基因的高效、安全递送仍然是基因治疗的关键。为了解决这个问题，通过自组装合成了一种以酶响应多肽修饰的聚酰胺胺（HPAA-肽-Fc）为核心、超支化聚甘油衍生物（CD-HPG）为壳的阳离子载体。获得的HPAA-肽-HPG可以与siPlk1形成致密的纳米复合物，从而证实基因的稳定负载和随后的靶向基因递送。并且纳米基因可以通过下调乳腺癌细胞中Plk1蛋白的表达来显着诱导细胞凋亡。此外，与聚乙烯亚胺相比，由于CD-HPG的屏蔽功能，通过溶血和细胞活力测定，HPAA-肽-HPG表现出优异的生物相容性，从而有利于增加体内给药时复合物的循环时间。这种高效、安全的基因传递复合物（HPAA-肽-HPG）为合理设计用于刺激响应性siRNA运输的阳离子超分子囊泡提供了一个很好的例子，这在癌症基因治疗中应该得到鼓励。
How to overcome multiple obstacles to achieve the efficient and safe delivery of therapeutic genes is still the key to gene therapy. To address this issue, a cationic carrier consisting of polyamide-amine (HPAA-peptide-Fc) modified by an enzyme-responsive polypeptide as the core and hyperbranched polyglycerol derivative (CD-HPG) as the shell was synthesized by self-assembly. The obtained HPAA-peptide-HPG could form the compact nanocomplex with siPlk1, thus confirming the stable load of genes and subsequent targeted gene delivery. And the nanogenes could significantly induce apoptotic effectviathe down-expression of Plk1 protein in breast cancer cells. Moreover, compared to polyethylenimine, HPAA-peptide-HPG exhibited superior biocompatibility through hemolysis and cell viability assays because of the shielding function of CD-HPG, thereby being beneficial to increasing the circulation time of the complex when administratedin vivo. Such an efficient and safe gene delivery complex (HPAA-peptide-HPG) presents a good example of rational design of cationic supramolecular vesicles for stimulus-responsive siRNA transport, which should be encouraged in cancer gene therapy.