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Homotypic Targeting Delivery of siRNA with Artificial Cancer Cells.
Advanced Healthcare Materials ( IF 10.0 ) Pub Date : 2020-03-17 , DOI: 10.1002/adhm.201900772
Lingmin Zhang 1 , Sai Deng 1 , Yanfen Zhang 1 , Qingsheng Peng 1 , Huan Li 1 , Ping Wang 1 , Xiaomei Fu 1 , Xueping Lei 1 , Aiping Qin 1 , Xiyong Yu 1
Affiliation  

The camouflage with cell membrane bestows nanoparticles with cell-like functions, such as specific recognition, long blood circulation, and immune escaping. For cancer therapy, the nanoparticles camouflaged with cancer cell membrane (CCM) from homologous cells show homotypic targeting delivery of small molecule compounds, photosensitizers, or enzymes to the tumors. However, effective gene therapy encounters difficulties by this approach due to the properties of nucleic acids. Herein, a cancer cell-like gene delivery system is developed using an excellent polymer poly(β-amino ester) (PBAE) to condense small interfering RNA (siRNA) (targeting to Plk1 gene) into nanoparticles (PBAE/siPlk1) as the core, which is further camouflaged with CCM. These novel biomimetic nanoparticles CCM/PBAE/siPlk1 (CCMPP) demonstrate highly specific targeting to homotypic cancer cells, effective downregulation of PLK1 level, and inducing apoptosis of cancer cells. Based on the homotypic binding adhesion molecules on the CCM, the cellular internalization and homotypic-targeting accumulation to the tumors are clearly improved. CCMPP induces highly efficient apoptosis of cancer cells both in vitro and in vivo and results in significant tumor inhibition. The artificial cancer cells with homotypic properties can serve as a biomimetic delivery system for cancer-targeted gene therapy.

中文翻译:

siRNA与人工癌细胞的同型靶向递送。

具有细胞膜的伪装赋予纳米颗粒具有细胞样功能,例如特异性识别,长时间的血液循环和免疫逃逸。对于癌症治疗,来自同源细胞的被癌细胞膜(CCM)伪装的纳米粒子表现出向小分子化合物,光敏剂或酶的同型靶向递送。然而,由于核酸的性质,有效的基因疗法通过这种方法遇到困难。在此,使用优异的高分子聚(β-氨基酯)(PBAE)将小分子干扰RNA(siRNA)(靶向Plk1基因)凝聚成纳米颗粒(PBAE / siPlk1),开发了癌细胞样基因传递系统。 ,而CCM则进一步对其进行了伪装。这些新颖的仿生纳米颗粒CCM / PBAE / siPlk1(CCMPP)展示了对同型癌细胞的高度特异性靶向,PLK1水平的有效下调以及诱导癌细胞的凋亡。基于CCM上的同型结合粘附分子,明显改善了肿瘤的细胞内在化和同型靶向积累。CCMPP在体外和体内诱导癌细胞的高效凋亡,并导致显着的肿瘤抑制作用。具有同型特性的人造癌细胞可以用作仿生传递系统,用于癌症靶向基因治疗。明显改善了肿瘤的细胞内在化和同型靶向积累。CCMPP在体外和体内诱导癌细胞的高效凋亡,并导致显着的肿瘤抑制作用。具有同型特性的人造癌细胞可以用作仿生传递系统,用于癌症靶向基因治疗。明显改善了肿瘤的细胞内在化和同型靶向积累。CCMPP在体外和体内诱导癌细胞的高效凋亡,并导致显着的肿瘤抑制作用。具有同型特性的人造癌细胞可以用作仿生传递系统,用于癌症靶向基因治疗。
更新日期:2020-03-17
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