Redox-Responsive Polysulfide-Based Biodegradable Organosilica Nanoparticles for Delivery of Bioactive Agents.
Redox-Responsive Polysulfide-Based Biodegradable Organosilica Nanoparticles for Delivery of Bioactive Agents.
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DOI：
10.1021/acsami.7b04351
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发表时间：
2017-06-28
影响因子：
9.5
通讯作者：
Ghandehari H
中科院分区：
文献类型：
--
作者：
Hadipour Moghaddam SP;Saikia J;Yazdimamaghani M;Ghandehari H
具有受控降解轮廓的二氧化硅纳米颗粒(SiO_2纳米颗粒)的设计和开发保证了具有预定载体消除轮廓的有效药物输送。在这项研究中，我们制备了一系列氧化还原响应型多硫化物基可生物降解纳米二氧化硅纳米颗粒，其多分散性较低，尺寸(平均直径为58±7、108±11、110±9、124±9和332±6 nm)、孔隙率和组成(二硫键和四硫键)不同。在8 mM谷胱甘肽(GSH)存在下，模拟细胞内还原条件，分析了纳米颗粒的降解动力学。结果表明，孔隙率和芯层组成对纳米颗粒的降解率起主导作用。其中，108 nm介孔二硫化物纳米粒子的降解率最高。透射电子显微镜显示，非多孔纳米粒子经历了表面侵蚀，而多孔纳米粒子在还原环境中同时经历了表面和体的侵蚀。评价了这些纳米粒子对RAW 264.7巨噬细胞的细胞毒作用。结果表明，这些纳米粒子的IC50值在2 33±42~70 5±17μg m L−1之间，当浓度小于12 5μg m L−1时，对巨噬细胞均无细胞毒作用，15 d内收集的降解产物经2 4h孵育后对同一巨噬细胞株无细胞毒性。在没有和存在8 mM GSH的情况下，考察了阿霉素(DOX)在108 nm介孔二硫化物纳米粒中的体外释放。结果表明，药物的释放依赖于细胞内还原条件。由于其易于合成和放大、坚固的结构以及控制尺寸、组成、释放和消除的能力，可生物降解的二氧化硅纳米颗粒为生物活性和显像剂的输送提供了一种替代平台。
Design and development of silica nanoparticles (SiO2 NPs) with a controlled degradation profile promises effective drug delivery with a predetermined carrier elimination profile. In this research, we fabricated a series of redox-responsive polysulfide-based biodegradable SiO2 NPs with low polydispersity and with variations in size (average diameters of 58 ± 7, 108 ± 11, 110 ± 9, 124 ± 9, and 332 ± 6 nm), porosity, and composition (disulfide vs tetrasulfide bonds). The degradation kinetics of the nanoparticles was analyzed in the presence of 8 mM glutathione (GSH), mimicking the intracellular reducing condition. Results indicate that porosity and core composition play the predominant roles in the degradation rate of these nanoparticles. The 108 nm mesoporous disulfide-based nanoparticles showed the highest degradation rate among all the synthesized nanoparticles. Transmission electron microscopy (TEM) reveals that nonporous nanoparticles undergo surface erosion, while porous nanoparticles undergo both surface and bulk erosion under reducing environment. The cytotoxicity of these nanoparticles in RAW 264.7 macrophages was evaluated. Results show that all these nanoparticles with the IC50 values ranging from 233 ± 42 to 705 ± 17 μg mL−1 do not have cytotoxic effect in macrophages at concentrations less than 125 μg mL−1. The degradation products of these nanoparticles collected within 15 days did not show cytotoxicity in the same macrophage cell line after 24 h of incubation. In vitro doxorubicin (DOX) release was examined in 108 nm mesoporous disulfide-based nanoparticles in the absence and presence of 8 mM GSH. It was shown that drug release depends on intracellular reducing conditions. Due to their ease of synthesis and scale up, robust structure, and the ability to control size, composition, release, and elimination, biodegradable SiO2 NPs provide an alternative platform for delivery of bioactive and imaging agents.
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影响因子：
11.4
作者：
Montero, Davide;Tachibana, Christine;Winther, Jakob Rahr;Appenzeller-Herzog, Christian
通讯作者：
Appenzeller-Herzog, Christian
影响因子：
29.4
作者：
Croissant, Jonas;Cattoen, Xavier;Durand, Jean-Olivier
通讯作者：
Durand, Jean-Olivier
影响因子：
17.4
作者：
Gustafson HH;Holt-Casper D;Grainger DW;Ghandehari H
通讯作者：
Ghandehari H
DOI：
10.1073/pnas.97.2.745
发表时间：
2000-01-18
影响因子：
11.1
作者：
Arunachalam, B;Phan, UT;Cresswell, P
通讯作者：
Cresswell, P
谷胱甘肽响应纳米载体作为靶向细胞内药物和基因递送的有前途的平台
影响因子：
10.8
作者：
Cheng, Ru;Feng, Fang;Zhong, Zhiyuan
通讯作者：
Zhong, Zhiyuan