TY - JOUR

T1 - In vitro and in vivo accumulation of magnetic nanoporous silica nanoparticles on implant materials with different magnetic properties

AU - Janßen, Hilke Catherina

AU - Warwas, Dawid Peter

AU - Dahlhaus, David

AU - Meißner, Jessica

AU - Taptimthong, Piriya

AU - Kietzmann, Manfred

AU - Behrens, Peter

AU - Reifenrath, Janin

AU - Angrisani, Nina

N1 - Funding information: This work was supported by the project “Implant-Directed Magnetic Drug Targeting: Antibiotic therapy of peri-implant infections”, Project Number: 280642759, which was funded by Deutsche Forschungsgemeinschaft (DE): RE 3456/2-1.

PY - 2018/11/27

Y1 - 2018/11/27

N2 - Background: In orthopedic surgery, implant-associated infections are still a major problem. For the improvement of the selective therapy in the infection area, magnetic nanoparticles as drug carriers are promising when used in combination with magnetizable implants and an externally applied magnetic field. These implants principally increase the strength of the magnetic field resulting in an enhanced accumulation of the drug loaded particles in the target area and therewith a reduction of the needed amount and the risk of undesirable side effects. In the present study magnetic nanoporous silica core-shell nanoparticles, modified with fluorophores (fluorescein isothiocyanate/FITC or rhodamine B isothiocyanate/RITC) and poly(ethylene glycol) (PEG), were used in combination with metallic plates of different magnetic properties and with a magnetic field. In vitro and in vivo experiments were performed to investigate particle accumulation and retention and their biocompatibility. Results: Spherical magnetic silica core-shell nanoparticles with reproducible superparamagnetic behavior and high porosity were synthesized. Based on in vitro proliferation and viability tests the modification with organic fluorophores and PEG led to highly biocompatible fluorescent particles, and good dispersibility. In a circular tube system martensitic steel 1.4112 showed superior accumulation and retention of the magnetic particles in comparison to ferritic steel 1.4521 and a Ti90Al6V4 control. In vivo tests in a mouse model where the nanoparticles were injected subcutaneously showed the good biocompatibility of the magnetic silica nanoparticles and their accumulation on the surface of a metallic plate, which had been implanted before, and in the surrounding tissue. Conclusion: With their superparamagnetic properties and their high porosity, multifunctional magnetic nanoporous silica nanoparticles are ideal candidates as drug carriers. In combination with their good biocompatibility in vitro, they have ideal properties for an implant directed magnetic drug targeting. Missing adverse clinical and histological effects proved the good biocompatibility in vivo. Accumulation and retention of the nanoparticles could be influenced by the magnetic properties of the implanted plates; a remanent martensitic steel plate significantly improved both values in vitro. Therefore, the use of magnetizable implant materials in combination with the magnetic nanoparticles has promising potential for the selective treatment of implant-associated infections.

AB - Background: In orthopedic surgery, implant-associated infections are still a major problem. For the improvement of the selective therapy in the infection area, magnetic nanoparticles as drug carriers are promising when used in combination with magnetizable implants and an externally applied magnetic field. These implants principally increase the strength of the magnetic field resulting in an enhanced accumulation of the drug loaded particles in the target area and therewith a reduction of the needed amount and the risk of undesirable side effects. In the present study magnetic nanoporous silica core-shell nanoparticles, modified with fluorophores (fluorescein isothiocyanate/FITC or rhodamine B isothiocyanate/RITC) and poly(ethylene glycol) (PEG), were used in combination with metallic plates of different magnetic properties and with a magnetic field. In vitro and in vivo experiments were performed to investigate particle accumulation and retention and their biocompatibility. Results: Spherical magnetic silica core-shell nanoparticles with reproducible superparamagnetic behavior and high porosity were synthesized. Based on in vitro proliferation and viability tests the modification with organic fluorophores and PEG led to highly biocompatible fluorescent particles, and good dispersibility. In a circular tube system martensitic steel 1.4112 showed superior accumulation and retention of the magnetic particles in comparison to ferritic steel 1.4521 and a Ti90Al6V4 control. In vivo tests in a mouse model where the nanoparticles were injected subcutaneously showed the good biocompatibility of the magnetic silica nanoparticles and their accumulation on the surface of a metallic plate, which had been implanted before, and in the surrounding tissue. Conclusion: With their superparamagnetic properties and their high porosity, multifunctional magnetic nanoporous silica nanoparticles are ideal candidates as drug carriers. In combination with their good biocompatibility in vitro, they have ideal properties for an implant directed magnetic drug targeting. Missing adverse clinical and histological effects proved the good biocompatibility in vivo. Accumulation and retention of the nanoparticles could be influenced by the magnetic properties of the implanted plates; a remanent martensitic steel plate significantly improved both values in vitro. Therefore, the use of magnetizable implant materials in combination with the magnetic nanoparticles has promising potential for the selective treatment of implant-associated infections.

KW - Biocompatibility

KW - Core-shell nanoparticles

KW - Drug targeting

KW - Ferritic steel

KW - Martensitic steel

KW - Mouse model

KW - Nanoporous silica

KW - PEGylation

KW - Superparamagnetic FeO

KW - NIH 3T3 Cells

KW - Silicon Dioxide/chemistry

KW - Biocompatible Materials/chemistry

KW - Humans

KW - Magnetite Nanoparticles/chemistry

KW - Prostheses and Implants

KW - Nanopores

KW - Hep G2 Cells

KW - Drug Carriers/chemistry

KW - Animals

KW - Female

KW - Mice

KW - Mice, Inbred BALB C

KW - Magnetic Fields

UR - http://www.scopus.com/inward/record.url?scp=85057217312&partnerID=8YFLogxK

U2 - 10.1186/s12951-018-0422-6

DO - 10.1186/s12951-018-0422-6

M3 - Article

C2 - 30482189

AN - SCOPUS:85057217312

VL - 16

JO - Journal of nanobiotechnology

JF - Journal of nanobiotechnology

SN - 1477-3155

M1 - 96

ER -