Distribution of Glutathione-Stabilized Gold Nanoparticles in Feline Fibrosarcomas and Their Role as a Drug Delivery System for Doxorubicin—Preclinical Studies in a Murine Model
Abstract
:1. Introduction
2. Results
3. Discussion
4. Materials and Methods
4.1. Cell Cultivation
4.2. Au-GSH and Dox Conjugated to Glutathione-Stabilized Gold Nanoparticles (Au-GSH-Dox) Preparation and Characterization
4.3. Animal Studies
4.3.1. Animal Housing
4.3.2. Au-GSH and Au-GSH-Dox Distribution and Efficacy Studies
4.4. ICP-MS Analyses
4.5. Confocal Microscopy
4.6. Histopathology and Immunohistochemistry
4.7. Statistical Analyses
Acknowledgments
Author Contributions
Conflicts of Interest
Abbreviations
Au-NP | gold nanoparticle |
Au-GSH | glutathione-stabilized gold nanoparticle |
Au-GSH-Dox | doxorubicin conjugated to glutathione-stabilized gold nanoparticles |
ALT | alanine transaminase |
AST | asparagine transaminase |
BUN | blood urea nitrogen |
DDS | drug delivery system |
DLS | dynamic light scattering |
Dox | doxorubicin |
FISS | feline injection-site sarcoma |
HE | hematoxylin and eosin |
HP | histopathology |
HPF | high power field |
ICP-MS | inductively-coupled plasma mass spectrometer |
IV | intravenous |
MDR | multidrug resistance |
MeOH | methanol |
MRP | multidrug resistance protein |
NaBH4 | sodium borohydride |
NaCl | Sodium chloride |
NaHCO3 | saturated sodium bicarbonate |
PBS | phosphate-buffered saline |
P-gp | P-glycoprotein |
SAXS | small angle X-ray scattering |
SD | standard deviation |
SEM | standard error of mean |
TAM | tumor-associated macrophages |
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Tested Compound | ID | Grading System of Fibrosarcoma 1 | Hemorrhages | Inflammation | Au-GSH Deposits | ||||
---|---|---|---|---|---|---|---|---|---|
Differentiation | Mitotic Count | Mitotic Score | Necrosis | Grade | |||||
NaCl | 93795 | 3 | 148 | 3 | 1 | III | Yes | 1 | No |
NaCl | 93864 | 3 | 103 | 3 | 3 | III | Yes | 0 | No |
NaCl | 93869 | 3 | 133 | 3 | 3 | III | Yes | 1 | No |
NaCl | 93870 | 3 | 90 | 3 | 3 | III | Yes | 3 | No |
NaCl | 93872 | 3 | 124 | 3 | 2 | III | Yes | 0 | No |
NaCl | 93873 | 3 | 144 | 3 | 3 | III | Yes | 1 | No |
NaCl | 93874 | 3 | 139 | 3 | 3 | III | Yes | 0 | No |
Au-GSH | 93862 | 3 | 113 | 3 | 1 | III | Yes | 0 | Peripherally |
Au-GSH | 93863 | 3 | 164 | 3 | 3 | III | Yes | 1 | Peripherally and in tumor within area of necrosis |
Au-GSH | 93866 | 3 | 121 | 3 | 2 | III | Yes | 0 | Peripherally |
Au-GSH | 93867 | 3 | 121 | 3 | 2 | III | Yes | 1 | Peripherally and in tumor within area of necrosis |
Au-GSH | 93871 | 3 | 191 | 3 | 3 | III | Yes | 1 | Peripherally and in tumor within area of necrosis |
Au-GSH | 93793 | 3 | 121 | 3 | 2 | III | Yes | 0 | Peripherally |
Au-GSH | 93794 | 3 | 116 | 3 | 2 | III | Yes | 3 | Peripherally and in tumor within area of necrosis |
Au-GSH-Dox | 93842 | 3 | 111 | 3 | 3 | III | Yes | 2 | Peripherally |
Au-GSH-Dox | 93843 | 3 | 99 | 3 | 3 | III | Yes | 3 | Peripherally and in tumor within area of necrosis |
Au-GSH-Dox | 93844 | 3 | 59 | 3 | 2 | III | Yes | 1 | Peripherally and in tumor within area of necrosis |
Au-GSH-Dox | 93868 | 3 | 124 | 3 | 3 | III | Yes | 1 | Peripherally |
Au-GSH-Dox | 93846 | 3 | 101 | 3 | 2 | III | Yes | 0 | Peripherally and in tumor within area of necrosis |
Au-GSH-Dox | 93847 | 3 | 142 | 3 | 2 | III | Yes | 0 | Peripherally and in tumor within area of necrosis |
Au-GSH-Dox | 93848 | 3 | 136 | 3 | 2 | III | Yes | 2 | Peripherally and in tumor wthin area of necrosis |
Au-GSH-Dox | 93849 | 3 | 84 | 3 | 3 | III | Yes | 3 | Peripherally |
Au-GSH-Dox | 93851 | 3 | 111 | 3 | 3 | III | Yes | 1 | Peripherally and in tumor within area of necrosis |
Au-GSH-Dox | 93858 | 3 | 115 | 3 | 3 | III | Yes | 0 | Peripherally and in tumor within area of necrosis |
Au-GSH-Dox | 93853 | 3 | 100 | 3 | 2 | III | Yes | 3 | Peripherally and in tumor within area of necrosis |
Au-GSH-Dox | 93788 | 3 | 54 | 3 | 2 | III | Yes | 1 | Peripherally and in tumor within area of necrosis |
Au-GSH-Dox | 93789 | 3 | 98 | 3 | 2 | III | Yes | 2 | Peripherally |
Dox | 93791 | 3 | 114 | 3 | 2 | III | Yes | 0 | No |
Dox | 93854 | 3 | 108 | 3 | 2 | III | Yes | 0 | No |
Dox | 93855 | 3 | 125 | 3 | 2 | III | Yes | 2 | No |
Dox | 93856 | 3 | 134 | 3 | 3 | III | Yes | 3 | No |
Dox | 93857 | 3 | 101 | 3 | 2 | III | Yes | 2 | No |
Dox | 93858 | 3 | 92 | 3 | 1 | III | Yes | 0 | No |
Dox | 93859 | 3 | 63 | 3 | 1 | III | Yes | 1 | No |
Dox | 93860 | 3 | 96 | 3 | 2 | III | Yes | 1 | No |
Dox | 93861 | 3 | 112 | 3 | 2 | III | Yes | 1 | No |
Dox | 93845 | 3 | 108 | 3 | 2 | III | Yes | 1 | No |
Dox | 93850 | 3 | 101 | 3 | 2 | III | Yes | 1 | No |
Dox | 93865 | 3 | 155 | 3 | 1 | III | Yes | 1 | No |
Dox | 93792 | 3 | 169 | 3 | 2 | III | Yes | 1 | No |
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Zabielska-Koczywąs, K.; Wojtalewicz, A.; Użarowska, E.; Klejman, A.; Wojtkowska, A.; Dolka, I.; Wojnicki, M.; Sobczak, K.; Wójcik, M.; Shen, H.; et al. Distribution of Glutathione-Stabilized Gold Nanoparticles in Feline Fibrosarcomas and Their Role as a Drug Delivery System for Doxorubicin—Preclinical Studies in a Murine Model. Int. J. Mol. Sci. 2018, 19, 1021. https://doi.org/10.3390/ijms19041021
Zabielska-Koczywąs K, Wojtalewicz A, Użarowska E, Klejman A, Wojtkowska A, Dolka I, Wojnicki M, Sobczak K, Wójcik M, Shen H, et al. Distribution of Glutathione-Stabilized Gold Nanoparticles in Feline Fibrosarcomas and Their Role as a Drug Delivery System for Doxorubicin—Preclinical Studies in a Murine Model. International Journal of Molecular Sciences. 2018; 19(4):1021. https://doi.org/10.3390/ijms19041021
Chicago/Turabian StyleZabielska-Koczywąs, Katarzyna, Anna Wojtalewicz, Ewelina Użarowska, Agata Klejman, Agata Wojtkowska, Izabella Dolka, Marek Wojnicki, Katarzyna Sobczak, Michał Wójcik, Haifa Shen, and et al. 2018. "Distribution of Glutathione-Stabilized Gold Nanoparticles in Feline Fibrosarcomas and Their Role as a Drug Delivery System for Doxorubicin—Preclinical Studies in a Murine Model" International Journal of Molecular Sciences 19, no. 4: 1021. https://doi.org/10.3390/ijms19041021