Department of Pathology and Genomic Medicine, The Methodist Hospital and Cancer Pathology Laboratory, The Methodist Hospital Research Institute, 6565 Fannin Street, Houston, TX 77030, USA.
Small. 2013 Oct 25;9(20):3477-84. doi: 10.1002/smll.201202694. Epub 2013 Apr 23.
Nanotechnology has often been applied in the development of targeted drug-delivery systems for the treatment of cancer. An ideal nanoscale system for drug delivery should be able to selectively deliver and rapidly release the carried therapeutic drug(s) in cancer cells and, more importantly, not react to off-target cells so as to eliminate unwanted toxicity on normal tissues. To reach this goal, a selective chemotherapeutic is formulated using a hollow gold nanosphere (HAuNS) equipped with a biomarker-specific aptamer (Apt), and loaded with the chemotherapy drug doxorubicin (DOX). The formed Apt-HAuNS-Dox, approximately 42 nm in diameter, specifically binds to lymphoma tumor cells and does not react to control cells that do not express the biomarker. Through aptamer-mediated selective cell binding, the Apt-HAuNS-Dox is internalized exclusively into the targeted tumor cells, and then released the DOX intracellularly. Of note, although the formed Apt-HAuNS-Dox is stable under normal biological conditions (pH 7.4), it appears ultrasensitive to pH change and rapidly releases 80% of the loaded DOX within 2 h at pH 5.0, a condition seen in cell lysosomes. Functional assays using cell mixtures show that the Apt-HAuNS-Dox selectively kills lymphoma tumor cells, but has no effect on the growth of the off-target cells in the same cultures, indicating that this ultra pH-sensitive Apt-HAuNS-Dox can selectively treat cancer through specific aptamer guidance, and will have minimal side effects on normal tissue.
纳米技术经常被应用于靶向药物输送系统的开发，以治疗癌症。一个理想的药物输送纳米系统应该能够选择性地将携带的治疗药物递送到癌细胞中，并迅速释放，更重要的是，不会与非靶细胞反应，以消除对正常组织的不必要毒性。为了达到这个目标，一种使用带有生物标志物特异性适体（Apt）的中空金纳米球（HAuNS）制备的选择性化疗药物被配方化，并负载化疗药物阿霉素（DOX）。形成的 Apt-HAuNS-DOX，直径约 42nm，特异性地与淋巴瘤肿瘤细胞结合，而不会与不表达生物标志物的对照细胞反应。通过适体介导的选择性细胞结合，Apt-HAuNS-DOX 被专门内化到靶肿瘤细胞中，然后将 DOX 释放到细胞内。值得注意的是，尽管形成的 Apt-HAuNS-DOX 在正常生理条件下（pH7.4）稳定，但它对 pH 变化非常敏感，在 pH5.0 下 2 小时内迅速释放 80%的负载 DOX，这种情况在细胞溶酶体中可见。使用细胞混合物进行的功能测定表明，Apt-HAuNS-DOX 选择性杀死淋巴瘤肿瘤细胞，但对同一培养物中靶外细胞的生长没有影响，这表明这种超 pH 敏感的 Apt-HAuNS-DOX 可以通过特异性适体引导选择性地治疗癌症，对正常组织的副作用最小。
