TY - JOUR
T1 - In vitro and in vivo radiotoxicity and biodistribution of thallium-201 delivered to cancer cells by Prussian blue nanoparticles
AU - Wulfmeier, Katarzyna
AU - Pellico Saez, Juan
AU - Machado, Pedro
AU - Carbajal, Maria
AU - Bakker, S
AU - T. M. de Rosales, Rafael
AU - Sunassee, Kavitha
AU - Blower, Philip
AU - Abbate, Vincenzo
AU - Terry, Samantha
PY - 2025/2/11
Y1 - 2025/2/11
N2 - Thallium-201 (t1/2 = 73 h) emits around 37 Auger and other secondary electrons per decay and is highly radiotoxic when internalised into cancer cells. However, the lack of effective chelators hinders its application in molecular radiotherapy. This study evaluates Prussian blue nanoparticles, coated with citric acid (201Tl-caPBNPs) or chitosan (201Tl-chPBNPs), as a 201Tl delivery vehicle compared with unbound 201Tl+. Cellular uptake and efflux kinetics, and radiotoxicity using clonogenic and H2AX DNA damage assays, were evaluated in vitro for both nanoparticle types. Subcellular localisation was also assessed using electron microscopy with energy dispersive X-ray spectroscopy. Biodistribution of 201Tl-chPBNPs was evaluated in vivo in mice bearing subcutaneous A549 tumour xenografts, using single photon computed tomography imaging and ex vivo tissue counting. Compared to unbound ²⁰¹Tl⁺, ²⁰¹Tl-chPBNPs showed higher cellular uptake, while ²⁰¹Tl-caPBNPs uptake was reduced. Both showed delayed efflux of ²⁰¹Tl from cancer cells. PBNPs pre-localised within cells enhanced the capture and retention of ²⁰¹Tl⁺ ions. Both types of PBNPs accumulated in cytoplasmic vesicular compartments and were not visible in nuclei. Furthermore, ²⁰¹Tl-radiolabelled chPBNPs but not 201Tl-caPBNPs showed significantly greater radiotoxicity than unbound 201Tl+ per Becquerel of radiotoxicity provided in media, resulting from their higher uptake and delayed efflux. However, when corrected for the greater activity accumulated in cells and delayed efflux, the radiotoxicity of 201Tl-chPBNPs was lower than that of unbound 201Tl+, possibly due to differences in subcellular localisation. These findings highlight the potential of chPBNPs for enhancing uptake and retention of 201Tl in cancer cells and development of targeted radionuclide therapy.
AB - Thallium-201 (t1/2 = 73 h) emits around 37 Auger and other secondary electrons per decay and is highly radiotoxic when internalised into cancer cells. However, the lack of effective chelators hinders its application in molecular radiotherapy. This study evaluates Prussian blue nanoparticles, coated with citric acid (201Tl-caPBNPs) or chitosan (201Tl-chPBNPs), as a 201Tl delivery vehicle compared with unbound 201Tl+. Cellular uptake and efflux kinetics, and radiotoxicity using clonogenic and H2AX DNA damage assays, were evaluated in vitro for both nanoparticle types. Subcellular localisation was also assessed using electron microscopy with energy dispersive X-ray spectroscopy. Biodistribution of 201Tl-chPBNPs was evaluated in vivo in mice bearing subcutaneous A549 tumour xenografts, using single photon computed tomography imaging and ex vivo tissue counting. Compared to unbound ²⁰¹Tl⁺, ²⁰¹Tl-chPBNPs showed higher cellular uptake, while ²⁰¹Tl-caPBNPs uptake was reduced. Both showed delayed efflux of ²⁰¹Tl from cancer cells. PBNPs pre-localised within cells enhanced the capture and retention of ²⁰¹Tl⁺ ions. Both types of PBNPs accumulated in cytoplasmic vesicular compartments and were not visible in nuclei. Furthermore, ²⁰¹Tl-radiolabelled chPBNPs but not 201Tl-caPBNPs showed significantly greater radiotoxicity than unbound 201Tl+ per Becquerel of radiotoxicity provided in media, resulting from their higher uptake and delayed efflux. However, when corrected for the greater activity accumulated in cells and delayed efflux, the radiotoxicity of 201Tl-chPBNPs was lower than that of unbound 201Tl+, possibly due to differences in subcellular localisation. These findings highlight the potential of chPBNPs for enhancing uptake and retention of 201Tl in cancer cells and development of targeted radionuclide therapy.
M3 - Article
SN - 1944-8244
JO - ACS Applied Materials and Interfaces
JF - ACS Applied Materials and Interfaces
ER -
