Using a chemotherapeutic agent, such as doxorubicin (DOX), with a natural agent, such as silibinin (Sili), is highly valuable to minimize systemic toxicity. However, Sili and DOX face disadvantages, such as low aqueous solubility and poor bioavailability. Here, we have engineered a drug delivery cargo by decorating carboxylated graphene oxide (cGO) with an aptamer, HB5, for simultaneous delivery of DOX and Sili as a combination therapy against MCF-7 and SK-BR-3 breast cancer cells. The resulting Apt-cGO displayed a typical sheet-like nanostructure with a broad surface. The maximum entrapment efficiency was 70.42% and 84.22% for Sili and DOX, respectively. When the Apt-cGO-DOX-Sili nanocomposites were selectively taken up by breast cancer cells, the interaction between cGO and drugs was cleaved, causing releasing both Sili and DOX into the tumor cells, respectively. Compared to free drugs, Apt-cGO-DOX-Sili nanocomposites displayed higher cytotoxicity in vitro. Apt-cGO-DOX-Sili nanocomposites potentially suppressed some cancer cell survival signals. They accelerated cell apoptosis and increased Rb levels as well as reduced Akt, mTOR, NF-κB, and CDK2 levels. In conclusion, the developed Apt-cGO-DOX-Sili can be suggested as a simple and efficient drug delivery approach for breast chemotherapy.

中文翻译：

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HB5适配体标记的氧化石墨烯用于阿霉素和水飞蓟宾的联合递送，以及乳腺癌的高效联合治疗

使用化学治疗剂，如多柔比星 (DOX) 和天然药物，如水飞蓟宾 (Sili)，对于最大限度地减少全身毒性非常有价值。然而，Sili和DOX面临水溶性低、生物利用度差等缺点。在这里，我们通过用适体 HB5 修饰羧化氧化石墨烯 (cGO) 来设计药物递送货物，用于同时递送 DOX 和 Sili 作为针对 MCF-7 和 SK-BR-3 乳腺癌细胞的联合疗法。由此产生的 Apt-cGO 显示出具有宽表面的典型片状纳米结构。Sili 和 DOX 的最大包封率分别为 70.42% 和 84.22%。当 Apt-cGO-DOX-Sili 纳米复合材料被乳腺癌细胞选择性摄取时，cGO 与药物之间的相互作用被切断，导致分别将 Sili 和 DOX 释放到肿瘤细胞中。与游离药物相比，Apt-cGO-DOX-Sili 纳米复合材料在体外表现出更高的细胞毒性。Apt-cGO-DOX-Sili 纳米复合材料可能会抑制一些癌细胞存活信号。它们加速细胞凋亡并增加 Rb 水平，同时降低 Akt、mTOR、NF-κB 和 CDK2 水平。总之，所开发的 Apt-cGO-DOX-Sili 可以作为一种简单有效的乳腺癌化疗药物输送方法。