College of Pharmacy, The University of Texas at Austin, Austin, TX 78712, USA.
Nanomedicine (Lond). 2012 Apr;7(4):475-91. doi: 10.2217/nnm.11.112. Epub 2012 Feb 2.
Previously, it was shown that treatment of tumor-bearing mice with an RNA replicase-based plasmid that produces dsRNA when transfected into tumor cells significantly inhibited the tumor growth. In the present study, the feasibility of further improving the anti-tumor activity of the RNA replicase-based plasmid by targeting it into tumors cells was evaluated.
MATERIAL & METHODS: An EGF-conjugated, polyethylene glycosylated cationic liposome was developed to deliver the RNA replicase-based plasmid, pSIN-β, into EGF receptor-overexpressing human breast cancer cells (MDA-MB-468) in vitro and in vivo.
Delivery of pSIN-β using the EGF receptor-targeted liposome more effectively controlled the growth of MDA-MB-468 tumors (and human epidermoid carcinoma A431 tumors) in mice than using untargeted liposome. The pSIN-β carried by the EGF receptor-targeted liposome caused the complete regression of MDA-MB-468 tumors in mice, probably due to the enhancement of its proapoptotic, antiproliferative and antiangiogenic activities.
Tumor-targeted RNA replicase-based plasmids hold a strong potential in tumor therapy.
先前的研究表明，转染到肿瘤细胞中能产生双链 RNA 的 RNA 复制酶质粒治疗荷瘤小鼠，能显著抑制肿瘤生长。本研究评估了将 RNA 复制酶质粒靶向肿瘤细胞以进一步提高其抗肿瘤活性的可行性。
设计了一种表皮生长因子（EGF）结合的聚乙二醇化阳离子脂质体，用于将 RNA 复制酶质粒 pSIN-β递送至 EGF 受体过表达的人乳腺癌细胞（MDA-MB-468）体外和体内。
与未靶向脂质体相比，使用 EGF 受体靶向脂质体递送 pSIN-β 能更有效地控制 MDA-MB-468 肿瘤（和人表皮样癌细胞 A431 肿瘤）在小鼠体内的生长。靶向 EGF 受体的脂质体携带的 pSIN-β 可使 MDA-MB-468 肿瘤在小鼠中完全消退，这可能是由于其促凋亡、抗增殖和抗血管生成活性增强所致。
肿瘤靶向 RNA 复制酶质粒在肿瘤治疗中具有很大的潜力。
