Fibrillar pharmacology of functionalized nanocellulose.
Fibrillar pharmacology of functionalized nanocellulose.
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DOI：
10.1038/s41598-020-79592-5
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发表时间：
2021-01-08
影响因子：
4.6
通讯作者：
McDevitt MR
中科院分区：
文献类型：
--
作者：
Wong S;Alidori S;Mello BP;Almeida BA;Ulmert D;Brendel MB;Scheinberg DA;McDevitt MR
纤维素纳米晶体（CNC）是来源于丰富的天然生物聚合物资源的线性有机纳米材料。CNC上伯羟基和仲羟基的策略性修饰分别引入胺基和碘基取代。使胺基（每克官能化CNC（fCNC）0.285 mmol胺）进一步与作为示踪剂的放射性金属负载螯合物或荧光染料反应，以评价fCNC的体内药代动力学特征。通过这种方式，这些纳米级大分子可以被共价官能化，并产生用于体内基因、药物和放射性核素递送的水溶性和生物相容性纤维状纳米平台。fCNC的透射电子显微镜显示每个颗粒的长度为162.4 ± 16.3 nm，直径为11.2 ± 1.52 nm，纵横比为16.4 ± 1.94（平均值± SEM），并使用原子力显微镜进行确认。大分子fCNC的尺寸排阻色谱法描述了纤维状分子行为，如通过后期洗脱小分子和官能化碳纳米管的典型保留时间所证明的。在体内，超过50%的静脉注射放射性标记的fCNC在给药后1小时内经尿液排泄，与其他刚性、高纵横比大分子观察到的药理学特征一致。fCNC的组织分布显示在给药后72小时在肾脏、肝脏和脾脏中蓄积（每克组织分别为14.6 ± 6.0、6.1 ± 2.6和7.7 ± 1.4%的注射活性）。共聚焦荧光显微镜揭示了这些靶组织汇细胞特异性积累。总之，我们的研究结果表明，功能化的纳米纤维素可用作肾脏的潜在药物递送平台。
Cellulose nanocrystals (CNC) are linear organic nanomaterials derived from an abundant naturally occurring biopolymer resource. Strategic modification of the primary and secondary hydroxyl groups on the CNC introduces amine and iodine group substitution, respectively. The amine groups (0.285 mmol of amine per gram of functionalized CNC (fCNC)) are further reacted with radiometal loaded-chelates or fluorescent dyes as tracers to evaluate the pharmacokinetic profile of the fCNC in vivo. In this way, these nanoscale macromolecules can be covalently functionalized and yield water-soluble and biocompatible fibrillar nanoplatforms for gene, drug and radionuclide delivery in vivo. Transmission electron microscopy of fCNC reveals a length of 162.4 ± 16.3 nm, diameter of 11.2 ± 1.52 nm and aspect ratio of 16.4 ± 1.94 per particle (mean ± SEM) and is confirmed using atomic force microscopy. Size exclusion chromatography of macromolecular fCNC describes a fibrillar molecular behavior as evidenced by retention times typical of late eluting small molecules and functionalized carbon nanotubes. In vivo, greater than 50% of intravenously injected radiolabeled fCNC is excreted in the urine within 1 h post administration and is consistent with the pharmacological profile observed for other rigid, high aspect ratio macromolecules. Tissue distribution of fCNC shows accumulation in kidneys, liver, and spleen (14.6 ± 6.0; 6.1 ± 2.6; and 7.7 ± 1.4% of the injected activity per gram of tissue, respectively) at 72 h post-administration. Confocal fluorescence microscopy reveals cell-specific accumulation in these target tissue sinks. In summary, our findings suggest that functionalized nanocellulose can be used as a potential drug delivery platform for the kidneys.
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DOI：
10.1016/j.omtn.2017.06.005
发表时间：
2017-09-15
期刊：
Molecular therapy. Nucleic acids
影响因子：
--
作者：
Chakraborty C;Sharma AR;Sharma G;Doss CGP;Lee SS
通讯作者：
Lee SS
影响因子：
9.5
作者：
Xu, Xuezhu;Liu, Fei;Wiesenborn, Dennis P.
通讯作者：
Wiesenborn, Dennis P.
影响因子：
16.6
作者：
Usov, Ivan;Nystroem, Gustav;Adamcik, Jozef;Handschin, Stephan;Schutz, Christina;Fall, Andreas;Bergstrom, Lennart;Mezzenga, Raffaele
通讯作者：
Mezzenga, Raffaele
影响因子：
3.7
作者：
McDevitt MR;Chattopadhyay D;Jaggi JS;Finn RD;Zanzonico PB;Villa C;Rey D;Mendenhall J;Batt CA;Njardarson JT;Scheinberg DA
通讯作者：
Scheinberg DA
影响因子：
7.1
作者：
Ruusunen, M;Vainionpää, J;Ahvenainen, R
通讯作者：
Ahvenainen, R