This study demonstrated the targeted delivery and controlled release of cisplatin drug molecules from doubly decorated mesoporous silica nanoparticles (MSNs), which were internally grafted with fluorescent conjugates and externally coated with polydopamine (PDA) and graphene oxide (GO) layers. The brush-like internal conjugates conferred fluorescent functionality and high capacity of cisplatin loading into MSNs, as well as contributing to a sustained release of the cisplatin through a porous channel with the assistance of external PDA layer. A consolidated double-layer formed by electrostatic interactions between the GO nanosheet and the PDA layer induced more controlled release kinetics which was well predicted by Higuchi model. In addition, Our MSNs exhibited stimuli (pH, NIR irradiation)-responsive controlled release as a potential chemo-photothermal agent against cancer cells. In a cell test, multifunctional MSNs showed a low toxicity itself, but gave a high cytotoxicity against human epithelial neuroblastoma cells (SH-SY5Y) after loading cisplatin. Notably, GO-wrapped MSNs exhibited very effective drug delivery because GO wrapping enhanced their dispensability in aqueous solution, photothermal heating effect, and efficient endocytosis into cells. Furthermore, monoclonal antibody (anti-human epidermal growth factor receptor)-conjugated MSNs showed a higher specificity, which resulted in more enhanced anticancer effects in vitro. The current study demonstrated a reliable synthesis of multifunctional MSNs, endowed with fluorescent imaging, stimuli-responsive controlled release, higher specificity, and efficient cytotoxicity toward cancer cells.

Statement of Significance

The current study demonstrated the reliable synthesis of multifunctional mesoporous silica nanoparticles (MSNs) with internal fluorescent conjugates and external polydopamine and graphene oxide (GO) layers. The combination of internal conjugates and external coating layers produced an effective pore closure effect, leading to controlled and sustained release of small drug molecules. Notably, GO wrapping improved the dispensability and cellular uptake of the MSNs, as well as enhanced drug-controlled release. Our multifunctional MSNs revealed very efficient drug delivery effects against human epithelial neuroblastoma cells by demonstrating several strengths: i) fluorescent imaging, ii) sustained and controlled release of small drug molecules, iii) efficient cellular uptake, cytotoxicity and specificity, and v) stimuli (pH, NIR irradiation)-responsive controlled release as a potential chemo-photothermal agent.

中文翻译：

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通过具有内部荧光共轭物和外部聚多巴胺和氧化石墨烯层的多功能介孔二氧化硅纳米粒子靶向和控制药物输送

这项研究证明了顺铂药物分子从双重修饰的介孔二氧化硅纳米粒子（MSNs）的靶向递送和控制释放，该分子内部荧光接枝了嫁接物，并在外部涂覆了聚多巴胺（PDA）和氧化石墨烯（GO）层。刷状内部共轭物赋予荧光功能和顺铂载入MSN的高容量，并有助于在外部PDA层的帮助下通过多孔通道持续释放顺铂。由GO纳米片和PDA层之间的静电相互作用形成的固结双层诱导了更多的控释动力学，Higuchi模型对此进行了很好的预测。此外，我们的MSN表现出刺激性（pH，NIR辐射）响应控制释放，作为针对癌细胞的潜在化学光热剂。在细胞测试中，多功能MSN本身显示出低毒性，但在加载顺铂后对人上皮神经母细胞瘤细胞（SH-SY5Y）具有高细胞毒性。明显地，GO包裹的MSN表现出非常有效的药物递送，因为GO包裹增强了其在水溶液中的可分配性，光热加热作用以及对细胞的有效内吞作用。此外，单克隆抗体（抗人表皮生长因子受体）偶联的MSNs显示出更高的特异性，从而导致更强的抗癌作用 但在加载顺铂后，对人上皮神经母细胞瘤细胞（SH-SY5Y）具有很高的细胞毒性。明显地，GO包裹的MSN表现出非常有效的药物递送，因为GO包裹增强了其在水溶液中的可分配性，光热加热作用以及对细胞的有效内吞作用。此外，单克隆抗体（抗人类表皮生长因子受体）偶联的MSNs显示出更高的特异性，从而导致更强的抗癌作用 但在加载顺铂后，对人上皮神经母细胞瘤细胞（SH-SY5Y）具有很高的细胞毒性。明显地，GO包裹的MSN表现出非常有效的药物递送，因为GO包裹增强了其在水溶液中的可分配性，光热加热作用以及对细胞的有效内吞作用。此外，单克隆抗体（抗人表皮生长因子受体）偶联的MSNs显示出更高的特异性，从而导致更强的抗癌作用体外。当前的研究表明多功能MSN的可靠合成，具有荧光成像，刺激响应控制释放，更高的特异性和对癌细胞的有效细胞毒性。

重要声明

当前的研究证明了具有内部荧光共轭物和外部聚多巴胺和氧化石墨烯（GO）层的多功能介孔二氧化硅纳米粒子（MSNs）的可靠合成。内部结合物和外部涂层的结合产生有效的孔封闭作用，导致小分子药物的受控和持续释放。明显地，GO包裹改善了MSN的可分配性和细胞摄取，以及增强的药物控制释放。我们的多功能MSN通过展示几种优势显示出对人上皮神经母细胞瘤细胞非常有效的药物递送作用：i）荧光成像，ii）药物分子的持续控制释放，iii）有效的细胞摄取，细胞毒性和特异性，以及v）刺激（ pH值