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
N1 - Publisher Copyright:
© 2025 The Authors. Published by American Chemical Society.
PY - 2025/3/5
Y1 - 2025/3/5
N2 - Thallium-201 (t1/2 = 73 h) emits around 37 Auger and other secondary electrons per decay and is highly radiotoxic when internalized 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 γH2AX DNA damage assays were evaluated in vitro for both nanoparticle types. Subcellular localization 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 tumor xenografts, using single photon computed tomography imaging and ex vivo tissue counting. Compared with unbound 201Tl+201Tl-chPBNPs showed higher cellular uptake, while 201Tl-caPBNP uptake was reduced. Both showed delayed efflux of 201Tl from cancer cells. PBNPs prelocalized within cells enhanced the capture and retention of 201Tl+ ions. Both types of PBNPs accumulated in cytoplasmic vesicular compartments and were not visible in the nuclei. Furthermore, 201Tl-radiolabeled 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 localization. These findings highlight the potential of chPBNPs for enhancing the 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 internalized 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 γH2AX DNA damage assays were evaluated in vitro for both nanoparticle types. Subcellular localization 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 tumor xenografts, using single photon computed tomography imaging and ex vivo tissue counting. Compared with unbound 201Tl+201Tl-chPBNPs showed higher cellular uptake, while 201Tl-caPBNP uptake was reduced. Both showed delayed efflux of 201Tl from cancer cells. PBNPs prelocalized within cells enhanced the capture and retention of 201Tl+ ions. Both types of PBNPs accumulated in cytoplasmic vesicular compartments and were not visible in the nuclei. Furthermore, 201Tl-radiolabeled 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 localization. These findings highlight the potential of chPBNPs for enhancing the uptake and retention of 201Tl in cancer cells and development of targeted radionuclide therapy.
KW - Tl
KW - Auger electron-emitters
KW - Prussian blue nanoparticles
KW - targeted radionuclide therapy
KW - thallium binding
UR - http://www.scopus.com/inward/record.url?scp=86000373847&partnerID=8YFLogxK
U2 - 10.1021/acsami.4c21700
DO - 10.1021/acsami.4c21700
M3 - Article
C2 - 39981690
AN - SCOPUS:86000373847
SN - 1944-8244
VL - 17
SP - 13577
EP - 13591
JO - ACS Applied Materials and Interfaces
JF - ACS Applied Materials and Interfaces
IS - 9
ER -
