Details
| Original language | English |
|---|---|
| Article number | 270 |
| Journal | Journal of nanobiotechnology |
| Volume | 21 |
| Issue number | 1 |
| Early online date | 17 Aug 2023 |
| Publication status | Published - Dec 2023 |
Abstract
Background: Implant infections caused by biofilm forming bacteria are a major threat in orthopedic surgery. Delivering antibiotics directly to an implant affected by a bacterial biofilm via superparamagnetic nanoporous silica nanoparticles could present a promising approach. Nevertheless, short blood circulation half-life because of rapid interactions of nanoparticles with the host’s immune system hinder them from being clinically used. The aim of this study was to determine the temporal in vivo resolution of magnetic nanoporous silica nanoparticle (MNPSNP) distribution and the effect of PEGylation and clodronate application using PET/CT imaging and gamma counting in an implant mouse model. Methods: PEGylated and non-PEGylated MNPSNPs were radiolabeled with gallium-68 (68Ga), implementing the chelator tris(hydroxypyridinone). 36 mice were included in the study, 24 mice received a magnetic implant subcutaneously on the left and a titanium implant on the right hind leg. MNPSNP pharmacokinetics and implant accumulation was analyzed in dependence on PEGylation and additional clodronate application. Subsequently gamma counting was performed for further final analysis. Results: The pharmacokinetics and biodistribution of all radiolabeled nanoparticles could clearly be visualized and followed by dynamic PET/CT imaging. Both variants of 68Ga-labeled MNPSNP accumulated mainly in liver and spleen. PEGylation of the nanoparticles already resulted in lower liver uptakes. Combination with macrophage depletion led to a highly significant effect whereas macrophage depletion alone could not reveal significant differences. Although MNPSNP accumulation around implants was low in comparison to the inner organs in PET/CT imaging, gamma counting displayed a significantly higher %I.D./g for the tissue surrounding the magnetic implants compared to the titanium control. Additional PEGylation and/or macrophage depletion revealed no significant differences regarding nanoparticle accumulation at the implantation site. Conclusion: Tracking of 68Ga-labeled nanoparticles in a mouse model in the first critical hours post-injection by PET/CT imaging provided a better understanding of MNPSNP distribution, elimination and accumulation. Although PEGylation increases circulation time, nanoparticle accumulation at the implantation site was still insufficient for infection treatment and additional efforts are needed to increase local accumulation.
Keywords
- Core–shell nanoparticles, Drug delivery systems, Implant imaging, Macrophage depletion, Magnetic targeting, PEGylation, PET imaging
ASJC Scopus subject areas
- Chemical Engineering(all)
- Bioengineering
- Medicine(all)
- Medicine (miscellaneous)
- Biochemistry, Genetics and Molecular Biology(all)
- Molecular Medicine
- Engineering(all)
- Biomedical Engineering
- Immunology and Microbiology(all)
- Applied Microbiology and Biotechnology
- Pharmacology, Toxicology and Pharmaceutics(all)
- Pharmaceutical Science
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In: Journal of nanobiotechnology, Vol. 21, No. 1, 270, 12.2023.
Research output: Contribution to journal › Article › Research › peer review
}
TY - JOUR
T1 - Preparation and PET/CT imaging of implant directed 68Ga-labeled magnetic nanoporous silica nanoparticles
AU - Polyak, Andras
AU - Harting, Heidi
AU - Angrisani, Nina
AU - Herrmann, Timo
AU - Ehlert, Nina
AU - Meißner, Jessica
AU - Willmann, Michael
AU - Al-Bazaz, Silav
AU - Ross, Tobias L.
AU - Bankstahl, Jens P.
AU - Reifenrath, Janin
N1 - Funding Information: First of all, the authors would like to remember Prof. Peter Behrens. Who was always full of new ideas and without whom this study would not have been possible. The authors would like to thank the LNQE (Laboratory of Nano- and Quantum Engineering, Leibniz University Hannover) for the use of their TEM equipment. Further the authors would like to thank Songül Noyun for nitrogen physisorption measurements and Katharina Nolte for thermogravimetric analysis. The authors would like to thank Anja Sander, Petra Felsch and Daniel Ahrens for their excellent technical support. Additionally, the authors would like to thank Dr. Bastian Welke for 3D printing of the placeholders. Funding Information: Open Access funding enabled and organized by Projekt DEAL. This work was supported by the DFG project “Implant-Directed Magnetic Drug Targeting: Antibiotic therapy of peri-implant infections”, project number: 280642759.
PY - 2023/12
Y1 - 2023/12
N2 - Background: Implant infections caused by biofilm forming bacteria are a major threat in orthopedic surgery. Delivering antibiotics directly to an implant affected by a bacterial biofilm via superparamagnetic nanoporous silica nanoparticles could present a promising approach. Nevertheless, short blood circulation half-life because of rapid interactions of nanoparticles with the host’s immune system hinder them from being clinically used. The aim of this study was to determine the temporal in vivo resolution of magnetic nanoporous silica nanoparticle (MNPSNP) distribution and the effect of PEGylation and clodronate application using PET/CT imaging and gamma counting in an implant mouse model. Methods: PEGylated and non-PEGylated MNPSNPs were radiolabeled with gallium-68 (68Ga), implementing the chelator tris(hydroxypyridinone). 36 mice were included in the study, 24 mice received a magnetic implant subcutaneously on the left and a titanium implant on the right hind leg. MNPSNP pharmacokinetics and implant accumulation was analyzed in dependence on PEGylation and additional clodronate application. Subsequently gamma counting was performed for further final analysis. Results: The pharmacokinetics and biodistribution of all radiolabeled nanoparticles could clearly be visualized and followed by dynamic PET/CT imaging. Both variants of 68Ga-labeled MNPSNP accumulated mainly in liver and spleen. PEGylation of the nanoparticles already resulted in lower liver uptakes. Combination with macrophage depletion led to a highly significant effect whereas macrophage depletion alone could not reveal significant differences. Although MNPSNP accumulation around implants was low in comparison to the inner organs in PET/CT imaging, gamma counting displayed a significantly higher %I.D./g for the tissue surrounding the magnetic implants compared to the titanium control. Additional PEGylation and/or macrophage depletion revealed no significant differences regarding nanoparticle accumulation at the implantation site. Conclusion: Tracking of 68Ga-labeled nanoparticles in a mouse model in the first critical hours post-injection by PET/CT imaging provided a better understanding of MNPSNP distribution, elimination and accumulation. Although PEGylation increases circulation time, nanoparticle accumulation at the implantation site was still insufficient for infection treatment and additional efforts are needed to increase local accumulation.
AB - Background: Implant infections caused by biofilm forming bacteria are a major threat in orthopedic surgery. Delivering antibiotics directly to an implant affected by a bacterial biofilm via superparamagnetic nanoporous silica nanoparticles could present a promising approach. Nevertheless, short blood circulation half-life because of rapid interactions of nanoparticles with the host’s immune system hinder them from being clinically used. The aim of this study was to determine the temporal in vivo resolution of magnetic nanoporous silica nanoparticle (MNPSNP) distribution and the effect of PEGylation and clodronate application using PET/CT imaging and gamma counting in an implant mouse model. Methods: PEGylated and non-PEGylated MNPSNPs were radiolabeled with gallium-68 (68Ga), implementing the chelator tris(hydroxypyridinone). 36 mice were included in the study, 24 mice received a magnetic implant subcutaneously on the left and a titanium implant on the right hind leg. MNPSNP pharmacokinetics and implant accumulation was analyzed in dependence on PEGylation and additional clodronate application. Subsequently gamma counting was performed for further final analysis. Results: The pharmacokinetics and biodistribution of all radiolabeled nanoparticles could clearly be visualized and followed by dynamic PET/CT imaging. Both variants of 68Ga-labeled MNPSNP accumulated mainly in liver and spleen. PEGylation of the nanoparticles already resulted in lower liver uptakes. Combination with macrophage depletion led to a highly significant effect whereas macrophage depletion alone could not reveal significant differences. Although MNPSNP accumulation around implants was low in comparison to the inner organs in PET/CT imaging, gamma counting displayed a significantly higher %I.D./g for the tissue surrounding the magnetic implants compared to the titanium control. Additional PEGylation and/or macrophage depletion revealed no significant differences regarding nanoparticle accumulation at the implantation site. Conclusion: Tracking of 68Ga-labeled nanoparticles in a mouse model in the first critical hours post-injection by PET/CT imaging provided a better understanding of MNPSNP distribution, elimination and accumulation. Although PEGylation increases circulation time, nanoparticle accumulation at the implantation site was still insufficient for infection treatment and additional efforts are needed to increase local accumulation.
KW - Core–shell nanoparticles
KW - Drug delivery systems
KW - Implant imaging
KW - Macrophage depletion
KW - Magnetic targeting
KW - PEGylation
KW - PET imaging
UR - http://www.scopus.com/inward/record.url?scp=85168258003&partnerID=8YFLogxK
U2 - 10.1186/s12951-023-02041-8
DO - 10.1186/s12951-023-02041-8
M3 - Article
C2 - 37592318
AN - SCOPUS:85168258003
VL - 21
JO - Journal of nanobiotechnology
JF - Journal of nanobiotechnology
SN - 1477-3155
IS - 1
M1 - 270
ER -