TY - JOUR
T1 - Short and long term, in vitro and in vivo correlations of cellular and tissue responses to mesoporous silicon nanovectors
AU - Martinez, Jonathan O.
AU - Boada, Christian
AU - Yazdi, Iman K.
AU - Evangelopoulos, Michael
AU - Brown, Brandon S.
AU - Liu, Xuewu
AU - Ferrari, Mauro
AU - Tasciotti, Ennio
N1 - Copyright:
Copyright 2013 Elsevier B.V., All rights reserved.
PY - 2013/5/27
Y1 - 2013/5/27
N2 - The characterization of nanomaterials and their influence on and interactions with the biology of cells and tissues are still partially unknown. Multistage nanovectors based on mesoporous silicon have been extensively studied for drug delivery, thermal heating, and improved diagnostic imaging. Here, the short- and long-term changes occurring in human cells upon the internalization of mesoporous silicon nanovectors (MSV) are analyzed. Using qualitative and quantitative techniques as well as in vitro and in vivo biochemical, cellular, and functional assays, it is demonstrated that MSV do not cause any significant acute or chronic effects on cells and tissues. In vitro cell toxicity and viability are analyzed, as well as the maintenance of cell phase cycling and the architecture upon the internalization of MSV. In addition, it is evaluated whether MSV produce any pro-inflammatory responses and its biocompatibility in vivo is studied. The biodistribution of MSV is followed using longitudinal in vivo imaging and organ accumulation is assessed using quantitative elemental and fluorescent techniques. Finally, a thorough pathological analysis of collected tissues demonstrates a mild transient systemic response in the liver that dissipates upon the clearance of particles. It is proposed that future endeavors aimed at understanding the toxicology of naked drug carriers should be designed to address their impact using in vitro and in vivo short- and long-term evaluations of systemic response. The toxicities accompanying mesoporous silicon nanovectors are evaluated using established in vitro and in vivo analogous techniques aiming to provide corresponding information on cellular and systemic levels over prolonged periods. In vivo longitudinal imaging demonstrates substantial accumulation of particles within the liver and spleen, which produce negligible cytotoxic effects, supporting their use for biomedical applications.
AB - The characterization of nanomaterials and their influence on and interactions with the biology of cells and tissues are still partially unknown. Multistage nanovectors based on mesoporous silicon have been extensively studied for drug delivery, thermal heating, and improved diagnostic imaging. Here, the short- and long-term changes occurring in human cells upon the internalization of mesoporous silicon nanovectors (MSV) are analyzed. Using qualitative and quantitative techniques as well as in vitro and in vivo biochemical, cellular, and functional assays, it is demonstrated that MSV do not cause any significant acute or chronic effects on cells and tissues. In vitro cell toxicity and viability are analyzed, as well as the maintenance of cell phase cycling and the architecture upon the internalization of MSV. In addition, it is evaluated whether MSV produce any pro-inflammatory responses and its biocompatibility in vivo is studied. The biodistribution of MSV is followed using longitudinal in vivo imaging and organ accumulation is assessed using quantitative elemental and fluorescent techniques. Finally, a thorough pathological analysis of collected tissues demonstrates a mild transient systemic response in the liver that dissipates upon the clearance of particles. It is proposed that future endeavors aimed at understanding the toxicology of naked drug carriers should be designed to address their impact using in vitro and in vivo short- and long-term evaluations of systemic response. The toxicities accompanying mesoporous silicon nanovectors are evaluated using established in vitro and in vivo analogous techniques aiming to provide corresponding information on cellular and systemic levels over prolonged periods. In vivo longitudinal imaging demonstrates substantial accumulation of particles within the liver and spleen, which produce negligible cytotoxic effects, supporting their use for biomedical applications.
KW - cancer therapy
KW - drug delivery
KW - mesoporous materials
KW - nanomaterials
KW - toxicity
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U2 - 10.1002/smll.201201939
DO - 10.1002/smll.201201939
M3 - Article
C2 - 23255523
AN - SCOPUS:84878075046
SN - 1613-6810
VL - 9
SP - 1722
EP - 1733
JO - Small
JF - Small
IS - 9-10
ER -