| Autor: |
Fach, Matthias, Fliedner, Frederikke P., Kempen, Paul J., Melander, Fredrik, Hansen, Anders E., Bruun, Linda M., Köster, Ulli, Sporer, Emanuel, Kjær, Andreas, Andresen, Thomas L., Jensen, Andreas I., Henriksen, Jonas R. |
| Zdroj: |
Advanced Healthcare Materials; May 2021, Vol. 10 Issue: 10 |
| Abstrakt: |
Local application of radioactive sources as brachytherapy is well established in oncology. This treatment is highly invasive however, due to the insertion of millimeter sized metal seeds. The authors report the development of a new concept for brachytherapy, based on gold‐palladium (AuPd) alloy nanoparticles, intrinsically radiolabeled with 103Pd. These are formulated in a carbohydrate‐ester based liquid, capable of forming biodegradable gel‐like implants upon injection. This allows for less invasive administration through small‐gauge needles. [103Pd]AuPd nanoparticles with sizes around 20 nm are prepared with radiolabeling efficiencies ranging from 79% to >99%. Coating with the hydrophobic polymer poly(N‐isopropylacrylamide) leads to nanoparticle diameters below 40 nm. Dispersing the nanoparticles in ethanol with water insoluble carbohydrate esters gives “nanogels”, a low viscosity liquid capable of solidifying upon injection into aqueous environments. Both nanoparticles and radioactivity are stably retained in the nanogel over 25 days (>99%) after formation in aqueous buffers. Animals bearing CT26 murine tumors are injected intratumorally with 25 MBq of the 103Pd‐nanogel, and display tumor growth delay and significantly increase median survival times compared with control groups. Excellent retention in the tumor of both the 103Pd and the nanoparticle matrix itself is observed, demonstrating a potential for replacing currently used brachytherapy seeds. As a new concept for brachytherapy, 103Pd‐radiolabeled gold‐palladium nanoparticles are hydrophobically coated and formulated in a carbohydrate‐based liquid. Upon injection, the liquid solidifies, forming brachytherapy‐seed like “nanogels”. The coating allows excellent retention of the nanoparticles in the gel, demonstrated both in vitro and in tumor‐bearing mice. Further, the 103Pd‐nanogels provide significant tumor growth delay and prolongation of survival times. |
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