Departments of Pharmacology and Radiology, Weill Cornell Medical College , New York, New York 10065, United States.
Nano Lett. 2017 Nov 8;17(11):7160-7168. doi: 10.1021/acs.nanolett.7b04209. Epub 2017 Oct 23.
Novel translational approaches based on clinical modular nanoplatforms are needed in order to treat solid cancers according to their discrete molecular features. In the present study, we show that the clinical nanopharmaceutical Ferumoxytol, which consists of a glucose-based coat surrounding an iron oxide core, could identify molecular characteristics of prostate cancer, corresponding to unique phases of the disease continuum. By affixing a targeting probe for the prostate-specific membrane antigen on its surface, the nanopharmaceutical was able to assess the functional state of the androgen receptor pathway via MRI, guiding therapy and delivering it with the same clinical nanoparticle. In order to simultaneously inhibit signaling from key oncogenic pathways of more advanced forms of prostate cancer, a single-agent therapy for early stage disease to inhibit DNA replication, as well as combination therapy with two drugs co-retained within the nanopharmaceutical's polymeric coating, were tested and resulted in complete tumor ablation. Recalcitrant and terminal forms of the disease were effectively treated with a nanopharmaceutical delivering a combination that upregulates endoplasmic reticulum stress and inhibits metastasis, thereby showing that this multifunctional nanoplatform can be used in the clinic for patient stratification, as well as precision treatment based on the individual's unique disease features.
为了根据实体瘤的离散分子特征进行治疗，需要基于临床模块化纳米平台的新型翻译方法。在本研究中，我们表明，由葡萄糖外壳包裹氧化铁核心组成的临床纳米药物 Ferumoxytol 可识别前列腺癌的分子特征，对应于疾病连续体的独特阶段。通过在其表面附着针对前列腺特异性膜抗原的靶向探针，纳米药物能够通过 MRI 评估雄激素受体途径的功能状态，指导治疗并通过相同的临床纳米颗粒进行递送。为了同时抑制更晚期前列腺癌的关键致癌途径的信号，对早期疾病进行了单一药物治疗以抑制 DNA 复制，以及用两种药物联合治疗并保留在纳米药物的聚合物涂层内，结果导致完全肿瘤消融。通过递送一种纳米药物来治疗难治性和终末期疾病，该药物上调内质网应激并抑制转移，从而表明这种多功能纳米平台可用于临床患者分层以及基于个体独特疾病特征的精准治疗。
