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Functionalized TiO2 nanoparticles labelled with 225Ac for targeted alpha radionuclide therapy
Edyta Cędrowska1, Marek Pruszynski1, Agnieszka Majkowska-Pilip1
11Institute of Nuclear Chemistry and Technology, Dorodna 16, 03-195 Warsaw, Poland.
Summary
Titanium dioxide nanoparticles effectively carry Actinium-225 for targeted radionuclide therapy. This novel approach shows promise for treating brain tumors by minimizing toxicity to healthy tissues.
Area of Science:
- Nuclear medicine
- Materials science
- Oncology
Background:
- Actinium-225 (Ac-225) is promising for radionuclide therapy due to its nuclear properties.
- A major challenge is preventing toxic release of radioactive daughters from traditional chelators.
- Titanium dioxide (TiO2) nanoparticles offer a potential solution as carriers for Ac-225 and its decay products.
Purpose of the Study:
- To develop and characterize TiO2 nanoparticles functionalized with Substance P (SP) for targeted delivery of Ac-225.
- To evaluate the stability and retention of Ac-225 and its daughters in the developed bioconjugates.
- To assess the in vitro efficacy of the Ac-225 loaded bioconjugates against glioma cells.
Main Methods:
- Synthesized 25 nm TiO2 nanoparticles functionalized with SP(5-11) peptide via a silan-PEG-NHS linker.
- Characterized nanoparticle-peptide conjugates using transmission electron microscopy (TEM), dynamic light scattering (DLS), and thermogravimetric analysis (TGA).
- Labeled the conjugates with Ac-225 via ion-exchange and evaluated Ac-225 and its daughter (Francium-221) retention in various media, alongside in vitro cytotoxicity assays on T98G glioma cells.
Main Results:
- TiO2-bioconjugate nanoparticles were synthesized with approximately 80 peptide molecules per nanoparticle.
- Ac-225 was retained with high efficiency (>97%) in phosphate-buffered saline (PBS), physiological salt, and cerebrospinal fluid (CSF) for up to 10 days.
- Minimal leaching (30%) of the first daughter, Francium-221 (Fr-221), was observed only in CSF after 10 days.
- The synthesized Ac-225-TiO2-PEG-SP(5-11) demonstrated significant in vitro cytotoxicity against T98G glioma cells.
Conclusions:
- TiO2 nanoparticles provide a stable platform for carrying Ac-225 and managing its radioactive daughters.
- The SP(5-11) functionalization enables targeted delivery to glioma cells.
- This Ac-225-loaded TiO2-bioconjugate represents a promising new radioconjugate for targeted radionuclide therapy of brain tumors.
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