Doxorubicin loaded silica nanorattles actively seek tumors with improved anti-tumor effects
Doxorubicin loaded silica nanorattles actively seek tumors with improved anti-tumor effects
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负载阿霉素的二氧化硅纳米摇铃积极寻找具有改善抗肿瘤效果的肿瘤
DOI：
10.1039/c2nr12094a
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发表时间：
2012-01-01
期刊：
影响因子：
6.7
通讯作者：
Tang, Fangqiong
中科院分区：
文献类型：
--
作者：
Gao, Fuping;Li, Linlin;Tang, Fangqiong
二氧化硅纳米片（SNs）已被证明是有前途的药物载体。为了进一步提高疗效和减少不良反应，主动靶向递送至肿瘤是必要的。在这项工作中，用肿瘤特异性靶向配体叶酸（FA）修饰的SNs被用作多柔比星（DOX）的载体（DOX-FA-SNs）。评价DOX-FA-SN的载药量、细胞毒性和体外人宫颈癌细胞（HeLa细胞）中的细胞摄取。DOX-FA-SN在人宫颈癌细胞（HeLa细胞）中显示出比DOX负载羧基（-COOH）和聚（乙二醇）（PEG）修饰的SN（分别为DOX-COOH-SN和DOX-PEG-SN）更高的细胞毒性。然而，与游离DOX相比，DOX-FA-SN在叶酸受体阴性的正常小鼠成纤维细胞（L929细胞）中显示出较低的细胞毒性。体内肿瘤靶向荧光成像表明FA-SN在荷有皮下HeLa细胞来源的异种移植肿瘤的裸鼠中的特异性肿瘤靶向和摄取。体内抗肿瘤实验表明，与游离DOX相比，DOX-FA-SN（10 mg/kg DOX）可显著抑制肿瘤生长并降低毒性。这些结果对开发和优化SN作为有效的细胞内递送和特异性肿瘤靶向载体具有重要意义。
Silica nanorattles (SNs) have proven to be promising vehicles for drug delivery. In order to further enhance efficacy and minimize adverse effects, active targeted delivery to tumors is necessary. In this work, SNs modified with a tumor specific targeting ligand, folic acid (FA), was used as carrier of doxorubicin (DOX) (DOX-FA-SNs). Drug loading, cytotoxicity and cellular uptake of DOX-FA-SNs in vitro in human cervical carcinoma cells (HeLa cells) were evaluated. DOX-FA-SNs showed a higher cytotoxicity in human cervical carcinoma cells (HeLa cells) than DOX loaded carboxyl (-COOH) and poly(ethylene glycol) (PEG) modified SNs (DOX-COOH-SNs and DOX-PEG-SNs, respectively). However, DOX-FA-SNs showed lower cytotoxicity in folate receptor negative normal mouse fibroblast cells (L929 cells) compared with free DOX. In vivo tumor-targeted fluorescence imaging indicated specific tumor targeting and uptake of FA-SNs in nude mice bearing subcutaneous HeLa cell-derived xenograft tumors. In vivo anti-tumor experiments demonstrated that DOX-FA-SNs (10 mg kg(-1) of DOX) significantly regressed the tumor growth and reduced toxicity compared with free DOX. These results have great significance in developing and optimizing SNs as effective intracellular delivery and specific tumor targeting vehicles.