Pirollo Kathleen F, Zon Gerald, Rait Antonina, Zhou Qi, Yu Wei, Hogrefe Richard, Chang Esther H
Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20057, USA.
Hum Gene Ther. 2006 Jan;17(1):117-24. doi: 10.1089/hum.2006.17.117.
The potential of short interfering RNA (siRNA) to be developed for therapeutic use against cancer depends on the availability of an efficient tumor-specific delivery vehicle. We have previously shown that a nanoscale nonviral liposome-based complex that includes an anti-transferrin receptor single-chain antibody fragment as the targeting moiety can, when systemically administered, specifically and efficiently target primary and metastatic tumors and deliver molecules useful in gene medicine, including plasmid DNA and antisense oligonucleotides. Here we explore the ability of this complex to deliver a fluorescein-labeled siRNA to tumor cells in vivo and examine the intracellular localization in vitro by confocal microscopy. We show that the immunoliposome--siRNA complex maintains its nanoscale size and, using three separate tumor models, can efficiently and specifically deliver siRNA to both primary and metastatic disease after systemic delivery, thus increasing the possibility for translating the potent effects of siRNA observed in vitro into clinically useful therapeutics.
将短干扰RNA（siRNA）开发用于癌症治疗的潜力取决于是否有高效的肿瘤特异性递送载体。我们之前已经表明，一种基于纳米级非病毒脂质体的复合物，其包含抗转铁蛋白受体单链抗体片段作为靶向部分，在全身给药时，可以特异性且高效地靶向原发性和转移性肿瘤，并递送基因治疗中有用的分子，包括质粒DNA和反义寡核苷酸。在此，我们探究这种复合物在体内将荧光素标记的siRNA递送至肿瘤细胞的能力，并通过共聚焦显微镜在体外检查细胞内定位。我们表明，免疫脂质体-siRNA复合物保持其纳米级尺寸，并且使用三种不同的肿瘤模型，在全身给药后可以高效且特异性地将siRNA递送至原发性和转移性疾病，从而增加了将体外观察到的siRNA的强效作用转化为临床有用治疗方法的可能性。
