Effective Intratumoral Retention of [103Pd]AuPd Alloy Nanoparticles Embedded in Gel-Forming Liquids Paves the Way for New Nanobrachytherapy

Matthias Fach, Frederikke P. Fliedner, Paul J. Kempen, Fredrik Melander, Anders E. Hansen, Linda M. Bruun, Ulli Köster, Emanuel Sporer, Andreas Kjær, Thomas L. Andresen, Andreas I. Jensen, Jonas R. Henriksen*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

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.

Original languageEnglish
JournalAdvanced Healthcare Materials
Number of pages11
ISSN2192-2640
DOIs
Publication statusAccepted/In press - 2021

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