Division of Nuclear Medicine, Department of Radiology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
J Biomed Nanotechnol. 2010 Apr;6(2):153-7. doi: 10.1166/jbn.2010.1111.
We reported recently that a three-component nanoparticle, consisting of a targeting antibody, a transfecting peptide and an 111In-antiRIalpha MORF antisense oligomer, provided Auger electron-mediated, antisense-mediated, cytotoxicity of cells in culture. We have now measured the cytotoxicity of the nanoparticle in culture with the 111In replaced by 125I, another attractive Auger electron emitter. The nanoparticle consisted of streptavidin linking the 125I labeled antiRIalpha mRNA antisense MORF oligomer, the tat transfecting peptide and the anti-Her2 Trastuzumab antibody. Cytotoxicity was evaluated by a clonogenic survival assay in BT-474 (Her2+) human breast cancer cells. In a dose escalation study, as measured by the surviving fraction, the cytotoxicity of tumor cells to the 125I-labeled antisense nanoparticle was significantly higher than that for the identical sense control. When compared with our previous study with 111In as label, a similar level of cytotoxicity was achieved but the observed minimal therapeutic dose for the 125I-labeled nanoparticle in BT-474 cells was lower than that for 111In-labeled nanoparticle in SK-BR-3 cells. Thus, a radiolabeled antisense MORF oligomer delivered into cells by a three-component nanoparticle is an effective vehicle for Auger radiotherapy when radiolabeled with 111In or 125I.
我们最近报道了一种由三部分组成的纳米颗粒，它由靶向抗体、转染肽和 111In-antiRIalpha MORF 反义寡核苷酸组成，为细胞提供了 Auger 电子介导的、反义介导的、细胞毒性。我们现在已经用 125I 取代了 111In 来测量纳米颗粒在培养物中的细胞毒性，125I 是另一种有吸引力的 Auger 电子发射体。纳米颗粒由链霉亲和素连接 125I 标记的抗 RIalpha mRNA 反义 MORF 寡核苷酸、tat 转染肽和抗 Her2 Trastuzumab 抗体组成。通过 BT-474（Her2+）人乳腺癌细胞的集落形成存活测定评估细胞毒性。在剂量递增研究中，以存活分数衡量，肿瘤细胞对 125I 标记的反义纳米颗粒的细胞毒性明显高于相同的正义对照。与我们以前用 111In 作为标记的研究相比，实现了类似的细胞毒性水平，但在 BT-474 细胞中，观察到的 125I 标记纳米颗粒的最小治疗剂量低于 SK-BR-3 细胞中 111In 标记纳米颗粒的最小治疗剂量。因此，用三部分纳米颗粒递送至细胞中的放射性标记反义 MORF 寡核苷酸是用 111In 或 125I 进行 Auger 放射治疗的有效载体。
