In Vitro and In Vivo Radiotoxicity and Biodistribution of Thallium-201 Delivered to Cancer Cells by Prussian Blue Nanoparticles

被引：0
|
作者：
Wulfmeier, Katarzyna M. [1 ]
Pellico, Juan [1 ,2 ]
Machado, Pedro [3 ,4 ]
Carbajal, M. Alejandra [3 ]
Bakker, Saskia E. [5 ]
de Rosales, Rafael T. M. [1 ]
Sunassee, Kavitha [1 ]
Blower, Philip J. [1 ]
Abbate, Vincenzo [6 ]
Terry, Samantha Y. A. [1 ]
机构：
[1] Kings Coll London, Sch Biomed Engn & Imaging Sci, London SE1 7EH, England
[2] CSIC, Inst Mat Sci Barcelona ICMAB, Bellaterra 08193, Spain
[3] Kings Coll London, Ctr Ultrastruct Imaging, London SE1 9RT, England
[4] Oxford Instruments Nanoanal, High Wycombe HP12 3SE, England
[5] Univ Warwick, Adv Bioimaging, Coventry CV4 7AL, England
[6] Kings Coll London, Inst Pharmaceut Sci, London SE1 9NH, England
来源：
ACS APPLIED MATERIALS & INTERFACES | 2025年 / 17卷 / 09期
基金：
英国惠康基金; 英国工程与自然科学研究理事会;
关键词：
Tl-201; Prussian blue nanoparticles; thallium binding; targeted radionuclide therapy; Auger electron-emitters; THERAPY; PRINCIPLES; ANALOGS; SHAPE; SIZE;
D O I：
10.1021/acsami.4c21700
中图分类号：
TB3 [工程材料学];
学科分类号：
0805 ; 080502 ;
摘要：
Thallium-201 (t(1/2) = 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 (Tl-201-caPBNPs) or chitosan (Tl-201-chPBNPs), as a Tl-201 delivery vehicle compared with unbound Tl-201(+). Cellular uptake and efflux kinetics and radiotoxicity using clonogenic and gamma H2AX 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 Tl-201-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 Tl-201(+), Tl-201-chPBNPs showed higher cellular uptake, while Tl-201-caPBNP uptake was reduced. Both showed delayed efflux of Tl-201 from cancer cells. PBNPs prelocalized within cells enhanced the capture and retention of Tl-201(+) ions. Both types of PBNPs accumulated in cytoplasmic vesicular compartments and were not visible in the nuclei. Furthermore, Tl-201-radiolabeled chPBNPs but not Tl-201-caPBNPs showed significantly greater radiotoxicity than unbound Tl-201(+) 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 Tl-201-chPBNPs was lower than that of unbound Tl-201(+), possibly due to differences in subcellular localization. These findings highlight the potential of chPBNPs for enhancing the uptake and retention of Tl-201 in cancer cells and development of targeted radionuclide therapy.
引用
收藏
页码：13577 / 13591
页数：15
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