Establishing the effects of mesoporous silica nanoparticle properties on in vivo disposition using imaging-based pharmacokinetics.
Establishing the effects of mesoporous silica nanoparticle properties on in vivo disposition using imaging-based pharmacokinetics.
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DOI：
10.1038/s41467-018-06730-z
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发表时间：
2018-10-31
影响因子：
16.6
通讯作者：
Brinker CJ
中科院分区：
文献类型：
--
作者：
Dogra P;Adolphi NL;Wang Z;Lin YS;Butler KS;Durfee PN;Croissant JG;Noureddine A;Coker EN;Bearer EL;Cristini V;Brinker CJ
由于不能在体内建立构效关系，基于纳米粒(NP)的药物传递的进展受到阻碍。在这里，我们使用稳定的、单一尺寸的、放射性标记的介孔二氧化硅纳米颗粒(MSN)，应用集成的SPECT/CT成像和数学建模方法来了解MSN尺寸、表面化学和给药途径对健康大鼠体内生物分布和清除动力学的综合影响。我们发现，颗粒尺寸从~32纳米增加到~142纳米会导致全身生物利用度单调下降，与给药途径无关，并相应地在肝脏和脾中蓄积。与具有相同大小和电荷但具有屏蔽胺(QA)的阳离子MSN相比，带有表面暴露的胺(PEI)的阳离子MSN由于快速隔离到肝和脾中而减少了循环。然而，QA的总排泄量比PEI和它们大小匹配的中性对应物(TM)要大。总体而言，我们提供了重要的预测性功能关联，以支持纳米药物的合理设计。由于对体内处置的物理化学性质的了解不足，纳米颗粒的应用受到限制。在这里，作者探索了大小，表面化学和给药对介孔二氧化硅纳米颗粒的生物处置的影响，基于图像的药代动力学。
The progress of nanoparticle (NP)-based drug delivery has been hindered by an inability to establish structure-activity relationships in vivo. Here, using stable, monosized, radiolabeled, mesoporous silica nanoparticles (MSNs), we apply an integrated SPECT/CT imaging and mathematical modeling approach to understand the combined effects of MSN size, surface chemistry and routes of administration on biodistribution and clearance kinetics in healthy rats. We show that increased particle size from ~32- to ~142-nm results in a monotonic decrease in systemic bioavailability, irrespective of route of administration, with corresponding accumulation in liver and spleen. Cationic MSNs with surface exposed amines (PEI) have reduced circulation, compared to MSNs of identical size and charge but with shielded amines (QA), due to rapid sequestration into liver and spleen. However, QA show greater total excretion than PEI and their size-matched neutral counterparts (TMS). Overall, we provide important predictive functional correlations to support the rational design of nanomedicines. Nanoparticle applications are limited by insufficient understanding of physiochemical properties on in vivo disposition. Here, the authors explore the influence of size, surface chemistry and administration on the biodisposition of mesoporous silica nanoparticles using image-based pharmacokinetics.
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影响因子：
4.9
作者：
Alexis F;Pridgen E;Molnar LK;Farokhzad OC
通讯作者：
Farokhzad OC
影响因子：
4.6
作者：
Brocato TA;Coker EN;Durfee PN;Lin YS;Townson J;Wyckoff EF;Cristini V;Brinker CJ;Wang Z
通讯作者：
Wang Z
表面修饰二氧化硅纳米粒子的生物分布和尿液排泄的体内研究
影响因子：
7.4
作者：
He, Xiaoxiao;Nie, Hailong;Zhang, Pengfei
通讯作者：
Zhang, Pengfei
影响因子：
3.8
作者：
HIRANO, K;HUNT, CA
通讯作者：
HUNT, CA
DOI：
10.1002/smll.201502119
发表时间：
2016-04-27
期刊：
Small (Weinheim an der Bergstrasse, Germany)
影响因子：
--
作者：
Butler KS;Durfee PN;Theron C;Ashley CE;Carnes EC;Brinker CJ
通讯作者：
Brinker CJ