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Enhanced Cancer Radiosensitization via Energy Transfer from Eu-Doped GdF3 Nanoparticles to Methylene Blue in X-ray Photodynamic Therapy

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Autor(es):
Isikawa, Mileni M. ; Muradova, Zeinaf ; Morris, Toby ; Lessa, Joao V. V. ; Borges, Fernanda H. ; Goncalves, Rogeria R. ; Berbeco, Ross I. ; Guidelli, Eder J.
Número total de Autores: 8
Tipo de documento: Artigo Científico
Fonte: ACS APPLIED MATERIALS & INTERFACES; v. 17, n. 37, p. 14-pg., 2025-09-04.
Resumo

We synthesized europium-doped gadolinium fluoride (GdF3:Eu) scintillating nanoparticles conjugated to methylene blue (MB) for singlet oxygen (1O2) generation in X-ray-induced photodynamic therapy (X-PDT). The impact of MB conjugation on GdF3:Eu nanoparticles (GdF@B) was analyzed, including size, polydispersity, and surface charge. Time-resolved photoluminescence analysis demonstrated that binding of MB to the nanoparticle surface is essential for enabling efficient resonant energy transfer (ET) from the GdF3:Eu core to the MB molecules. ET efficiencies >= 97% were obtained. 1O2 production exhibited energy- and dose-dependent behavior under varying radiation conditions. MTT assays demonstrated relative toxicity to LLC lung cancer mouse cells, while maintaining good tolerability in A549 human cancer cells. Clonogenic assays showed significant cytotoxicity in A549 cells only after X-ray exposure, confirming a reduced clonogenic survival. Survival fraction curves were analyzed using the linear-quadratic model, the sensitization enhancement factor, and the dose enhancement factor, highlighting the contributions of both the high atomic number of GdF3:Eu cores and 1O2 generation. The findings indicate that GdF@B enables deep-tissue ROS generation, overcoming light penetration limitations in traditional PDT. Additionally, these nanoparticles show potential to enhance radiotherapy efficacy in both conventional fractionated protocols and advanced radiosurgery techniques, offering a promising cancer treatment nanoplatform. (AU)

Processo FAPESP: 21/00786-0 - Desenvolvimento de nanodispositivos teranósticos com propriedades dosimétricas para aplicações em física médica
Beneficiário:Éder José Guidelli
Modalidade de apoio: Auxílio à Pesquisa - Regular
Processo FAPESP: 21/08111-2 - Materiais conversores de luz à base de terras raras: marcadores luminescentes, sensores e amplificadores ópticos
Beneficiário:Hermi Felinto de Brito
Modalidade de apoio: Auxílio à Pesquisa - Temático
Processo FAPESP: 24/21657-2 - Do Oxigênio aos Raios X: Diferentes Abordagens da Nanotecnologia para o Tratamento do Câncer
Beneficiário:Éder José Guidelli
Modalidade de apoio: Auxílio à Pesquisa - Regular