pH sensitive chitosan-mesoporous silica nanoparticles for targeted delivery of a ruthenium complex with enhanced anticancer effects
pH sensitive chitosan-mesoporous silica nanoparticles for targeted delivery of a ruthenium complex with enhanced anticancer effects
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pH敏感的壳聚糖-介孔二氧化硅纳米粒子，用于靶向递送具有增强抗癌作用的钌络合物
DOI：
10.1039/c6dt03783f
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发表时间：
2016-01-01
影响因子：
4
通讯作者：
Lin, Jianguo
中科院分区：
文献类型：
--
作者：
Lv, Gaochao;Qiu, Ling;Lin, Jianguo
纳米载体被广泛用于向肿瘤递送药物，并且其开发正在稳步进行。在这项研究中，pH敏感的介孔二氧化硅纳米载体，RuNHC@MSNs-CTS-Biotin（CTS =壳聚糖），被开发用于钌（II）N-杂环卡宾（RuNHC）络合物的靶向递送和控制释放。RuNHC@MSNs-CTS-生物素纳米颗粒由涂覆有壳聚糖-生物素（CTS-生物素）缀合物的负载RuNHC的介孔二氧化硅纳米颗粒（MSNs）组成。CTS将RuNHC复合物捕获在中孔内，生物素用作靶向配体以改善特异性细胞摄取。RuNHC@MSNs-CTS-生物素的粒径约为90 nm，zeta电位为12.0 mV，RuNHC负载量为26.31%。RuNHC@MSNs-CTS-Biotin对RuNHC的释放具有pH依赖性，在pH 5.0时释放率为59.71%，而在中性条件（pH 7.4）下几乎不释放。其体外细胞摄取和抗癌活性表明RuNHC@MSNs-CTS-Biotin可以通过生物素受体介导的内吞作用选择性地内化到癌细胞中，这导致与RuNHC复合物相比的抗癌活性显著提高。这种多功能纳米载体系统为开发精确可控的癌症治疗提供了一个有前途的平台。
Nanocarriers are widely used for delivering drugs to tumors and their development is progressing steadily. In this study, a pH sensitive mesoporous silica nanocarrier, RuNHC@MSNs-CTS-Biotin (CTS = chitosan), is developed for the targeted delivery and controlled release of a ruthenium(II) N-heterocyclic carbene (RuNHC) complex. The RuNHC@MSNs-CTS-Biotin nanoparticles were composed of RuNHC loaded mesoporous silica nanoparticles (MSNs) coated with chitosan-biotin (CTS-Biotin) conjugates. CTS traps the RuNHC complex inside the mesopores and biotin is used as a targeting ligand to improve specific cell uptake. The particle size of RuNHC@MSNs-CTS-Biotin was around 90 nm with a zeta potential of 12.0 mV and the RuNHC loading capacity was 26.31%. The release of RuNHC from RuNHC@MSNs-CTS-Biotin was in a pH-dependent manner, and it exhibited a 59.71% terminal release ratio at pH 5.0, but almost no release under neutral conditions (pH 7.4). Its in vitro cellular uptake and anticancer activity revealed that RuNHC@MSNs-CTS-Biotin could be selectively internalized in cancer cells by biotin recep-tor-mediated endocytosis and this resulted in a significant improvement in anticancer activities as compared with the RuNHC complex. This multifunctional nanocarrier system provides a promising platform for the development of precisely controllable cancer therapy.