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

Abstract

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.

Authors:
 [1];  [2];  [1];  [3];  [4];  [5];  [6];  [7];  [5];  [5];  [8];  [9];  [1];  [3];  [10];  [11]
  1. Houston Methodist Research Inst., Houston, TX (United States). Mathematics in Medicine Program
  2. Univ. of New Mexico, Albuquerque, NM (United States). Dept. of Biochemistry and Molecular Biology
  3. (United States). Dept. of Imaging Physics
  4. Univ. of New Mexico, Albuquerque, NM (United States). Dept. of Internal Medicine
  5. Univ. of New Mexico, Albuquerque, NM (United States). Center for Micro-Engineered Materials. Chemical and Biological Engineering
  6. (SNL-NM), Albuquerque, NM (United States). Dept. of Nanobiology
  7. Univ. of New Mexico, Albuquerque, NM (United States). Center for Micro-Engineered Materials. Cancer Research and Treatment Center. Molecular Genetics and Microbiology
  8. Sandia National Lab. (SNL-NM), Albuquerque, NM (United States). Applied Optical and Plasma Science
  9. Univ. of New Mexico, Albuquerque, NM (United States). Dept. of Pathology
  10. Univ. of New Mexico, Albuquerque, NM (United States). Center for Micro-Engineered Materials. Chemical and Biological Engineering. Cancer Research and Treatment Center. Molecular Genetics and Microbiology
  11. (SNL-NM), Albuquerque, NM (United States). Self-Assembled Materials Dept.
Publication Date:
Research Org.:
Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Houston Methodist Research Inst., Houston, TX (United States); Univ. of Texas MD Anderson Cancer Center, Houston, TX (United States); Univ. of New Mexico, Albuquerque, NM (United States)
Sponsoring Org.:
USDOE National Nuclear Security Administration (NNSA); SNL Laboratory Directed Research and Development (LDRD) Program; Defense Threat Reduction Agency (DTRA) (United States); National Inst. of Health (NIH) (United States); National Science Foundation (NSF)
OSTI Identifier:
1492391
Report Number(s):
SAND2018-9984J
Journal ID: ISSN 2041-1723; 667799
Grant/Contract Number:  
NA0003525; DTRA1002713506; DTRA100279003; U54CA210181; 1R01CA222007; 1R01CA226537; 1U01CA213759; 1U01CA196403; P50GM085273; DMS-1562068; DMS-1716737
Resource Type:
Journal Article: Accepted Manuscript
Journal Name:
Nature Communications
Additional Journal Information:
Journal Volume: 9; Journal ID: ISSN 2041-1723
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
English
Subject:
77 NANOSCIENCE AND NANOTECHNOLOGY; 60 APPLIED LIFE SCIENCES; drug delivery; imaging techniques and agents; nanoparticles; nanotechnology in cancer; scientific data

Citation Formats

Dogra, Prashant, Adolphi, Natalie L., Wang, Zhihui, Univ. of Texas MD Anderson Cancer Center, Houston, TX, Lin, Yu-Shen, Butler, Kimberly S., Sandia National Lab., Durfee, Paul N., Croissant, Jonas G., Noureddine, Achraf, Coker, Eric N., Bearer, Elaine L., Cristini, Vittorio, Univ. of Texas MD Anderson Cancer Center, Houston, TX, Brinker, C. Jeffrey, and Sandia National Lab. Establishing the effects of mesoporous silica nanoparticle properties on in vivo disposition using imaging-based pharmacokinetics. United States: N. p., 2018. Web. doi:10.1038/s41467-018-06730-z.
Dogra, Prashant, Adolphi, Natalie L., Wang, Zhihui, Univ. of Texas MD Anderson Cancer Center, Houston, TX, Lin, Yu-Shen, Butler, Kimberly S., Sandia National Lab., Durfee, Paul N., Croissant, Jonas G., Noureddine, Achraf, Coker, Eric N., Bearer, Elaine L., Cristini, Vittorio, Univ. of Texas MD Anderson Cancer Center, Houston, TX, Brinker, C. Jeffrey, & Sandia National Lab. Establishing the effects of mesoporous silica nanoparticle properties on in vivo disposition using imaging-based pharmacokinetics. United States. doi:10.1038/s41467-018-06730-z.
Dogra, Prashant, Adolphi, Natalie L., Wang, Zhihui, Univ. of Texas MD Anderson Cancer Center, Houston, TX, Lin, Yu-Shen, Butler, Kimberly S., Sandia National Lab., Durfee, Paul N., Croissant, Jonas G., Noureddine, Achraf, Coker, Eric N., Bearer, Elaine L., Cristini, Vittorio, Univ. of Texas MD Anderson Cancer Center, Houston, TX, Brinker, C. Jeffrey, and Sandia National Lab. Wed . "Establishing the effects of mesoporous silica nanoparticle properties on in vivo disposition using imaging-based pharmacokinetics". United States. doi:10.1038/s41467-018-06730-z. https://www.osti.gov/servlets/purl/1492391.
@article{osti_1492391,
title = {Establishing the effects of mesoporous silica nanoparticle properties on in vivo disposition using imaging-based pharmacokinetics},
author = {Dogra, Prashant and Adolphi, Natalie L. and Wang, Zhihui and Univ. of Texas MD Anderson Cancer Center, Houston, TX and Lin, Yu-Shen and Butler, Kimberly S. and Sandia National Lab. and Durfee, Paul N. and Croissant, Jonas G. and Noureddine, Achraf and Coker, Eric N. and Bearer, Elaine L. and Cristini, Vittorio and Univ. of Texas MD Anderson Cancer Center, Houston, TX and Brinker, C. Jeffrey and Sandia National Lab.},
abstractNote = {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.},
doi = {10.1038/s41467-018-06730-z},
journal = {Nature Communications},
issn = {2041-1723},
number = ,
volume = 9,
place = {United States},
year = {2018},
month = {10}
}

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