Hamilton Amanda M, Aidoudi-Ahmed Sallouha, Sharma Shweta, Kotamraju Venkata R, Foster Paula J, Sugahara Kazuki N, Ruoslahti Erkki, Rutt Brian K
Robarts Research Institute, University of Western Ontario, 1151 Richmond St N, London, ON, N6A 5B7, Canada.
Cancer Research Center, Sanford-Burnham Medical Research Institute, La Jolla, CA, USA.
J Mol Med (Berl). 2015 Sep;93(9):991-1001. doi: 10.1007/s00109-015-1279-x. Epub 2015 Apr 14.
Metastasis is the main killer in cancer; consequently, there is great interest in novel approaches to prevent and treat metastatic disease. Brain metastases are particularly deadly, as the protection of the blood-brain barrier obstructs the passage of common anticancer drugs. This study used magnetic resonance imaging (MRI) to investigate the therapeutic effects of nanoparticles coated with a tumor-penetrating peptide (iRGD) against a preclinical model of breast cancer brain metastasis. Single doses of iRGD nanoparticle were administered intravenously, and the effect on tumor growth was observed over time. iRGD nanoparticles, when applied in the early stages of metastasis development, strongly inhibited tumor progression. Overall, this study demonstrated for the first time that a single dose of iRGD nanoparticle can have a significant effect on metastatic tumor progression and nonproliferative cancer cell retention when applied early in course of tumor development. These data suggest that iRGD nanoparticles may be useful in preventatively reducing metastasis after a cancer diagnosis has been established.
bSSFP MRI can be used to track nonproliferative iron-labeled cells and tumor development over time. iRGD-NW, when applied early, has a significant effect on metastatic tumor progression. Retained signal voids represent a subpopulation of nonproliferating tumor cells. Reduced cell retention and tumor burden show a role for iRGD-NW in metastasis prevention. iRGD target is universally expressed; thus, iRGD-NW should be clinically translatable.
转移是癌症的主要杀手；因此，人们对预防和治疗转移性疾病的新方法非常感兴趣。脑转移尤其致命，因为血脑屏障的保护作用阻碍了常用抗癌药物的通过。本研究使用磁共振成像（MRI）来研究涂有肿瘤穿透肽（iRGD）的纳米颗粒对乳腺癌脑转移临床前模型的治疗效果。静脉注射单剂量iRGD纳米颗粒，并随时间观察其对肿瘤生长的影响。iRGD纳米颗粒在转移发展的早期应用时，能强烈抑制肿瘤进展。总体而言，本研究首次证明单剂量iRGD纳米颗粒在肿瘤发展过程早期应用时，可对转移性肿瘤进展和非增殖性癌细胞滞留产生显著影响。这些数据表明，iRGD纳米颗粒可能有助于在癌症诊断确立后预防性地减少转移。
bSSFP MRI可用于随时间追踪非增殖性铁标记细胞和肿瘤发展情况。iRGD-NW在早期应用时，对转移性肿瘤进展有显著影响。保留信号空洞代表非增殖性肿瘤细胞亚群。细胞滞留减少和肿瘤负担减轻表明iRGD-NW在转移预防中发挥作用。iRGD靶点普遍表达；因此，iRGD-NW应可进行临床转化应用。
