Establishing the effects of mesoporous silica nanoparticle properties on in vivo disposition using imaging-based pharmacokinetics

被引:206
作者
Dogra, Prashant [1 ]
Adolphi, Natalie L. [2 ]
Wang, Zhihui [1 ,3 ]
Lin, Yu-Shen [4 ]
Butler, Kimberly S. [5 ,6 ,7 ]
Durfee, Paul N. [5 ,8 ]
Croissant, Jonas G. [5 ,6 ]
Noureddine, Achraf [5 ,6 ]
Coker, Eric N. [9 ]
Bearer, Elaine L. [10 ]
Cristini, Vittorio [1 ,3 ]
Brinker, C. Jeffrey [5 ,6 ,8 ,11 ]
机构
[1] Houston Methodist Res Inst, Math Med Program, Houston, TX 77030 USA
[2] Univ New Mexico, Dept Biochem & Mol Biol, Albuquerque, NM 87131 USA
[3] Univ Texas MD Anderson Canc Ctr, Dept Imaging Phys, Houston, TX 78701 USA
[4] Univ New Mexico, Dept Internal Med, Albuquerque, NM 87131 USA
[5] Univ New Mexico, Ctr Microengn Mat, Albuquerque, NM 87131 USA
[6] Univ New Mexico, Chem & Biol Engn, Albuquerque, NM 87131 USA
[7] Sandia Natl Labs, Dept Nanobiol, Albuquerque, NM 87123 USA
[8] Univ New Mexico, Canc Res & Treatment Ctr, Mol Genet & Microbiol, Albuquerque, NM 87131 USA
[9] Sandia Natl Labs, Appl Opt & Plasma Sci, Albuquerque, NM 87185 USA
[10] Univ New Mexico, Dept Pathol, Albuquerque, NM 87131 USA
[11] Sandia Natl Labs, Self Assembled Mat Dept, POB 5800, Albuquerque, NM 87185 USA
基金
美国国家科学基金会; 美国国家卫生研究院;
关键词
SUPPORTED LIPID-BILAYERS; DRUG-DELIVERY; SURFACE-CHEMISTRY; URINARY-EXCRETION; PROTEIN CORONA; BIODISTRIBUTION; SIZE; CLEARANCE; CANCER; DOXORUBICIN;
D O I
10.1038/s41467-018-06730-z
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 similar to 32- to similar 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.
引用
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页数:14
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