Synthesis Optimization of BaGdF5:x%Tb3+ Nanophosphors for Tunable Particle Size.

X-ray photodynamic therapy (XPDT) is aimed at the treatment of deep-located malignant tumors thanks to the high penetration depth of X-rays. In XPDT therapy, it is necessary to use materials that effectively absorb X-rays and convert them into visible radiation-nanophosphors. Rare-earth elements, fluorides, in particular, doped BaGdF5, are known to serve as efficient nanophosphor. On the other hand, the particle size of nanophosphors has a crucial impact on biodistribution, cell uptake, and cytotoxicity. In this work, we investigated various Tb:Gd ratios in the range from 0.1 to 0.5 and optimized the terbium content to achieve the maximum luminescence under X-ray excitation. The effect of temperature, composition of the ethylene glycol/water solvent, and the synthesis technique (solvothermal and microwave) on the size of the nanophosphors was explored. It was found that the synthesis techniques and the solvent composition had the greatest influence on the averaged particle size. By varying these two parameters, it is possible to tune the size of the nanophosphor particles, which make them suitable for biomedical applications.

The Rare-Earth Elements Doping of BaGdF5 Nanophosphors for X-ray Photodynamic Therapy.

It is known that the initiation of photodynamic therapy (PDT) in deep-seated tumors requires the use of X-rays to activate the reactive oxygen species generation in deep tissues. The aim of this paper is to synthesize X-ray nanophosphors and analyze their structural and luminescence characteristics to push the PDT process deep into the body. The article deals with BaGdF5:Eu3+, BaGdF5:Sm3+, and BaGdF5:Tb3+ nanophosphors synthesized using microwave synthesis. It is found that the nanoparticles are biocompatible and have sizes 5-17 nm. However, according to the analysis of X-ray excited optical luminescence, BaGdF5:Sm3+ nanophosphors will not be effective for treating deep-seated tumors. Thus, BaGdF5:Eu3+ and BaGdF5:Tb3+ nanoparticles meet the requirements for the subsequent production of nanocomposites based on them that can be used in X-ray photodynamic therapy.

BaGdF5 Nanophosphors Doped with Different Concentrations of Eu3+ for Application in X-ray Photodynamic Therapy.

X-ray photodynamic therapy (XPDT) has been recently considered as an efficient alternative to conventional radiotherapy of malignant tissues. Nanocomposites for XPDT typically consist of two components-a nanophosphor which re-emits X-rays into visible light that in turn is absorbed by the second component, a photosensitizer, for further generation of reactive oxygen species. In this study, BaGdF5 nanophosphors doped with different Eu:Gd ratios in the range from 0.01 to 0.50 were synthesized by the microwave route. According to transmission electron microscopy (TEM), the average size of nanophosphors was ~12 nm. Furthermore, different coatings with amorphous SiO2 and citrates were systematically studied. Micro-CT imaging demonstrated superior X-ray attenuation and sufficient contrast in the liver and the spleen after intravenous injection of citric acid-coated nanoparticles. In case of the SiO2 surface, post-treatment core-shell morphology was verified via TEM and the possibility of tunable shell size was reported. Nitrogen adsorption/desorption analysis revealed mesoporous SiO2 formation characterized by the slit-shaped type of pores that should be accessible for methylene blue photosensitizer molecules. It was shown that SiO2 coating subsequently facilitates methylene blue conjugation and results in the formation of the BaGdF5: 10% Eu3+@SiO2@MB nanocomposite as a promising candidate for application in XPDT.

Nanomaterials for Deep Tumor Treatment.

According to statistics, cancer is the second leading cause of death in the world. Thus, it is important to solve this medical and social problem by developing new effective methods for cancer treatment. An alternative to more well-known approaches, such as radiotherapy and chemotherapy, is photodynamic therapy (PDT), which is limited to the shallow tissue penetration (< 1 cm) of visible light. Since the PDT process can be initiated in deep tissues by X-ray irradiation (X-ray induced PDT, or XPDT), it has a great potential to treat tumors in internal organs. The article discusses the principles of therapies. The main focus is on various nanoparticles used with or without photosensitizers, which allow the conversion of X-ray irradiation into UV-visible light. Much attention is given to the synthesis of nanoparticles and analysis of their characteristics, such as size and spectral features. The results of in vitro and in vivo experiments are also discussed.

Nanocomposites for X-Ray Photodynamic Therapy.

Photodynamic therapy (PDT) has long been known as an effective method for treating surface cancer tissues. Although this technique is widely used in modern medicine, some novel approaches for deep lying tumors have to be developed. Recently, deeper penetration of X-rays into tissues has been implemented, which is now known as X-ray photodynamic therapy (XPDT). The two methods differ in the photon energy used, thus requiring the use of different types of scintillating nanoparticles. These nanoparticles are known to convert the incident energy into the activation energy of a photosensitizer, which leads to the generation of reactive oxygen species. Since not all photosensitizers are found to be suitable for the currently used scintillating nanoparticles, it is necessary to find the most effective biocompatible combination of these two agents. The most successful combinations of nanoparticles for XPDT are presented. Nanomaterials such as metal-organic frameworks having properties of photosensitizers and scintillation nanoparticles are reported to have been used as XPDT agents. The role of metal-organic frameworks for applying XPDT as well as the mechanism underlying the generation of reactive oxygen species are discussed.