Progress in the development of nanosensitizers for X-ray-induced photodynamic therapy

Ren, Xu-Dong; Hao, Xiu-Yun; Li, Hongcai; Ke, Mei‐Rong; Zheng, Biyuan; Huang, Jian‐Dong

doi:10.1016/j.drudis.2018.05.029

Cited by 66 publications

(50 citation statements)

References 70 publications

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“…In PDT, a large part of visible light is absorbed by the photosensitizer which produces singlet oxygen, known as the PDT type II reaction [ 3 ]. In contrast, when X-PDT is used, only a small fraction of the X-ray emitted photons will be converted into scintillations [ 21 , 22 ]. Indeed, the interaction between material and high energy photons depends on the Z atomic number id est electronic density and incident energy [ 4 , 21 ].…”

Section: Discussionmentioning

confidence: 99%

“…A breakthrough strategy to treat GBM via nanomedicine and X-ray has been suggested by combining the principles of radiotherapy and PDT, both clinically proven modalities, while maintaining their main benefits and decreasing their drawbacks. The principle of the so-named X-ray-induced PDT (X-PDT) is based on the conversion of X-ray photons into visible photons, known as X-ray excited optical luminescence, from the nanoscintillator embedded in the nanoparticle and linked to the photosensitizer, which, in turn, produces singlet oxygen and other oxygen reactive species [ 21 , 22 ]. X-PDT proof-of-concept with nanoparticles was first introduced by Cheng and Wang, who described simultaneous radiation and X-ray-induced photodynamic effects [ 23 ].…”

Section: Introductionmentioning

confidence: 99%

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Terbium-Based AGuIX-Design Nanoparticle to Mediate X-ray-Induced Photodynamic Therapy

et al. 2021

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X-ray-induced photodynamic therapy is based on the energy transfer from a nanoscintillator to a photosensitizer molecule, whose activation leads to singlet oxygen and radical species generation, triggering cancer cells to cell death. Herein, we synthesized ultra-small nanoparticle chelated with Terbium (Tb) as a nanoscintillator and 5-(4-carboxyphenyl succinimide ester)-10,15,20-triphenyl porphyrin (P1) as a photosensitizer (AGuIX@Tb-P1). The synthesis was based on the AGuIX@ platform design. AGuIX@Tb-P1 was characterised for its photo-physical and physico-chemical properties. The effect of the nanoparticles was studied using human glioblastoma U-251 MG cells and was compared to treatment with AGuIX@ nanoparticles doped with Gadolinium (Gd) and P1 (AGuIX@Gd-P1). We demonstrated that the AGuIX@Tb-P1 design was consistent with X-ray photon energy transfer from Terbium to P1. Both nanoparticles had similar dark cytotoxicity and they were absorbed in a similar rate within the cells. Pre-treated cells exposure to X-rays was related to reactive species production. Using clonogenic assays, establishment of survival curves allowed discrimination of the impact of radiation treatment from X-ray-induced photodynamic effect. We showed that cell growth arrest was increased (35%-increase) when cells were treated with AGuIX@Tb-P1 compared to the nanoparticle doped with Gd.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Terbium-Based AGuIX-Design Nanoparticle to Mediate X-ray-Induced Photodynamic Therapy

et al. 2021

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“…It requires nanoparticles exhibiting appropriated physical properties to establish energy transduction from the nanoscintillator to the PS, a high scintillation quantum yield and an optimal energy transfer from the scintillator onto the PS [48,49]. However, one of the biggest X-PDT pitfall is that, only a small fraction of the X-ray emitted photons will be converted into scintillations [50]. In addition, X-PDT has been studied in preclinical conditions, with X-ray energies ranging from dozen to a few hundred keV.…”

Section: Nanoscintillators Would Increase Pdt Efficacymentioning

confidence: 99%

Can Cerenkov Light Really Induce an Effective Photodynamic Therapy?

et al. 2020

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Photodynamic therapy (PDT) is a promising therapeutic strategy for cancers where surgery and radiotherapy cannot be effective. PDT relies on the photoactivation of photosensitizers, most of the time by lasers to produced reactive oxygen species and notably singlet oxygen. The major drawback of this strategy is the weak light penetration in the tissues. To overcome this issue, recent studies proposed to generate visible light in situ with radioactive isotopes emitting charged particles able to produce Cerenkov radiation. In vitro and preclinical results are appealing, but the existence of a true, lethal phototherapeutic effect is still controversial. In this article, we have reviewed previous original works dealing with Cerenkov-induced PDT (CR-PDT). Moreover, we propose a simple analytical equation resolution to demonstrate that Cerenkov light can potentially generate a photo-therapeutic effect, although most of the Cerenkov photons are emitted in the UV-B and UV-C domains. We suggest that CR-PDT and direct UV-tissue interaction act synergistically to yield the therapeutic effect observed in the literature. Moreover, adding a nanoscintillator in the photosensitizer vicinity would increase the PDT efficacy, as it will convert Cerenkov UV photons to light absorbed by the photosensitizer.

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“…Photoluminescent CaF 2 :Ln NPs have been studied by several groups in the fields of biomedical diagnostics and therapeutics [ 20 , 21 , 22 , 23 ], as CaF 2 :Ln NPs can act as a source of visible-range photons, similar to other formulations of NP which enable imaging within biological tissues [ 15 , 16 ]. The same emitted photons can also photocatalyze specific chemical reactions, producing toxic species to kill local cells in a process commonly known as photodynamic therapy (PDT) [ 50 , 51 , 52 ]. One of the most prominent applications of CaF 2 :Ln NPs is in two-photon near-IR to visible energy conversion for deep tissue diagnostic and therapeutic applications.…”

Section: Resultsmentioning

confidence: 99%

Synthesis of Radioluminescent CaF2:Ln Core, Mesoporous Silica Shell Nanoparticles for Use in X-ray Based Theranostics

et al. 2020

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X-ray radiotherapy is a common method of treating cancerous tumors or other malignant lesions. The side effects of this treatment, however, can be deleterious to patient quality of life if critical tissues are affected. To potentially lower the effective doses of radiation and negative side-effects, new classes of nanoparticles are being developed to enhance reactive oxygen species production during irradiation. This report presents the synthesis and radiotherapeutic efficacy evaluation of a new nanoparticle formulation designed for this purpose, composed of a CaF2 core, mesoporous silica shell, and polyethylene glycol coating. The construct was additionally doped with Tb and Eu during the CaF2 core synthesis to prepare nanoparticles (NPs) with X-ray luminescent properties for potential application in fluorescence imaging. The mesoporous silica shell was added to provide the opportunity for small molecule loading, and the polyethylene glycol coating was added to impart aqueous solubility and biocompatibility. The potential of these nanomaterials to act as radiosensitizers for enhancing X-ray radiotherapy was supported by reactive oxygen species generation assays. Further, in vitro experiments indicate biocompatibility and enhanced cellular damage during X-ray radiotherapy.

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Progress in the development of nanosensitizers for X-ray-induced photodynamic therapy

Cited by 66 publications

References 70 publications

Terbium-Based AGuIX-Design Nanoparticle to Mediate X-ray-Induced Photodynamic Therapy

Terbium-Based AGuIX-Design Nanoparticle to Mediate X-ray-Induced Photodynamic Therapy

Can Cerenkov Light Really Induce an Effective Photodynamic Therapy?

Synthesis of Radioluminescent CaF2:Ln Core, Mesoporous Silica Shell Nanoparticles for Use in X-ray Based Theranostics

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