Mesoporous Silica Nanoparticles Coated by Layer-by-Layer Self-assembly Using Cucurbit[7]uril for in Vitro and in Vivo Anticancer Drug Release

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• 作者：Qing-Lan Li ; Yanfang Sun ; Yu-Long Sun ; Jijie Wen ; Yue Zhou ; Qi-Ming Bing ; Lyle D. Isaacs ; Yinghua Jin ; Hui Gao ; Ying-Wei Yang
• 刊名：Chemistry of Materials
• 出版年：2014
• 出版时间：November 25, 2014
• 年：2014
• 卷：26
• 期：22
• 页码：6418-6431
• 全文大小：901K
• ISSN：1520-5002

文摘

Mesoporous silica nanoparticles (MSNs) are promising solid supports for controlled anticancer drug delivery. Herein, we report biocompatible layer-by-layer (LbL) coated MSNs (LbL-MSNs) that are designed and crafted to release encapsulated anticancer drugs, e.g., doxorubicin hydrochloride (DOX), by changing the pH or by adding competitive agents. The LbL coating process comprises bis-aminated poly(glycerol methacrylate)s (BA-PGOHMAs) and cucurbit[7]uril (CB[7]), where CB[7] serves as a molecular bridge holding two different bis-aminated polymeric layers together by means of host鈥揼uest interactions. This integrated nanosystem is tuned to respond under specific acidic conditions or by adding adamantaneamine hydrochloride (AH), attributed to the competitive binding of hydronium ions or AH to CB[7] with BA-PGOHMAs. These LbL-MSN hybrids possess excellent biostability, negligible premature drug leakage at pH 7.4, and exceptional stimuli-responsive drug release performance. The pore sizes of the MSNs and bis-aminated compounds (different carbon numbers) of BA-PGOHMAs have been optimized to provide effective integrated nanosystems for the loading and release of DOX. Significantly, the operating pH for the controlled release of DOX matches the acidifying endosomal compartments of HeLa cancer cells, suggesting that these hybrid nanosystems are good candidates for autonomous anticancer drug nanocarriers actuated by intracellular pH changes without any invasive external stimuli. The successful cellular uptake and release of cargo, e.g., propidium iodide (PI), in human breast cancer cell line MDA-231 from PI-loaded LbL-MSNs have been confirmed by confocal laser scanning microscopy (CLSM), while the cytotoxicities of DOX-loaded LbL-MSNs have been quantified by the Cell Counting Kit-8 (CCK-8) viability assay against HeLa cell lines and fibroblast L929 cell lines. The uptake of DOX-loaded LbL-MSNs by macrophages can be efficiently reduced by adding biocompatible hydrophilic poly(ethylene glycol) or CB[7] without destroying the capping. In vivo tumor-growth inhibition experiments with BALB/c nude mice demonstrated a highly efficient tumor-growth inhibition rate of DOX-loaded LbL-MSNs, suggesting that the novel type of LbL-MSN materials hold great potentials in anticancer drug delivery.