Recent Progress and Trends in X-ray-Induced Photodynamic Therapy with Low Radiation Doses

Abstract

The prominence of photodynamic therapy (PDT) in treating superficial skin cancer inspires innovative solutions for its congenitally deficient shadow penetration of the visible-light excitation. X-ray-induced photodynamic therapy (X-PDT) has been proven to be a successful technique in reforming the conventional PDT for deep-seated tumors by creatively utilizing penetrating X-rays as external excitation sources and has witnessed rapid developments over the past several years. Beyond the proof-of-concept demonstration, recent advances in X-PDT have exhibited a trend of minimizing X-ray radiation doses to quite low values. As such, scintillating materials used to bridge X-rays and photosensitizers play a significant role, as do diverse well-designed irradiation modes and smart strategies for improving the tumor microenvironment. Here in this review, we provide a comprehensive summary of recent achievements in X-PDT and highlight trending efforts using low doses of X-ray radiation. We first describe the concept of X-PDT and its relationships with radiodynamic therapy and radiotherapy and then dissect the mechanism of X-ray absorption and conversion by scintillating materials, reactive oxygen species evaluation for X-PDT, and radiation side effects and clinical concerns on X-ray radiation. Finally, we discuss a detailed overview of recent progress regarding low-dose X-PDT and present perspectives on possible clinical translation. It is expected that the pursuit of low-dose X-PDT will facilitate significant breakthroughs, both fundamentally and clinically, for effective deep-seated cancer treatment in the near future.

Catalytic nanotechnology of X-ray photodynamics for cancer treatments

“…[296][297][298] Therefore, combination therapy has become a new development trend to overcome the shortcomings of single therapies. [299][300][301][302][303][304][305][306] Sun's team designed a multifunctional nanocarrier, T-TKNPVP, consisting of angiopep-2 (Ang) modified Ang-PEG-DSPE and TK-bridged PEG-TK-PTX conjugated compounds, as shown in Fig. 25(b, d and e).…”

“…Therefore, combination therapy has become a new development trend to overcome the shortcomings of single therapies. 299–306 Sun's team designed a multifunctional nanocarrier, T-TKNPVP, consisting of angiopep-2 (Ang) modified Ang-PEG-DSPE and TK-bridged PEG-TK-PTX conjugated compounds, as shown in Fig. 25(b, d and e). 307 Active targeting of X-PDT and cascade ROS-enhanced chemotherapy were achieved using this nanosystem.…”

Enhancement of Light and X-ray Charging in Persistent Luminescence Nanoparticle Scintillators Zn2SiO4:Mn2+, Yb3+, Li+

“…Photodynamic therapy (PDT) has been used in clinical cancer treatment as a less invasive, low toxicity, and highly selective treatment modality . Typically, PDT works by activating a photosensitizer with the appropriate wavelength of visible light in the presence of surrounding tissue oxygen to produce cytotoxic reactive oxygen species (ROS) such as singlet oxygen ( 1 O 2 ) to combat cancer cells. , However, due to the poor tissue penetration of visible light, extracorporeal irradiation cannot activate photosensitizers located in deep tissue tumors, thus limiting the therapeutic depth range of PDT. , Considering the high tissue penetration of X-rays, X-ray induced photodynamic therapy (X-PDT) was first proposed in 2006 by Chen and Zhang for the treatment of deep tissue tumors . X-PDT involves the use of an energy transducer to transfer X-ray energy to visible light emission, which activates adjacent photosensitizers to trigger the PDT process while simultaneously combining the radiotherapy (RT) process of X-rays to enhance the treatment effect. ,− To facilitate the delivery of the photosensitizer to the tumor site, transducers loaded with photosensitizers are required to be 20–200 nm nanoparticles to satisfy the enhanced permeability and retention (EPR) effect in the tumor. , In addition, to reduce radiation damage to normal tissues and to improve the efficacy of X-PDT, researchers have experimented with various efficient nanoparticle transducers, including conventional scintillator materials − and long persistent luminescent materials. , Long persistent luminescent nanoparticle scintillators (PLNS) have the unique property of continuing to emit visible light for a period of time after cessation of X-ray excitation .…”

“…1 Typically, PDT works by activating a photosensitizer with the appropriate wavelength of visible light in the presence of surrounding tissue oxygen to produce cytotoxic reactive oxygen species (ROS) such as singlet oxygen ( 1 O 2 ) to combat cancer cells. 2,3 However, due to the poor tissue penetration of visible light, 4 extracorporeal irradiation cannot activate photosensitizers located in deep tissue tumors, thus limiting the therapeutic depth range of PDT. 5,6 Considering the high tissue penetration of X-rays, X-ray induced photodynamic therapy (X-PDT) was first proposed in 2006 by Chen and Zhang for the treatment of deep tissue tumors.…”

Targeted photodynamic neutralization of SARS-CoV-2 mediated by singlet oxygen

“…Due to the unique physicochemical properties of 1 O 2 , namely its short lifetime and diffusion distance (~ 3 μm in viable cells which can be translated into a diffusion distance of ~ 150 nm) [11][12][13][14], CALI and PDT can achieve precise elimination of target molecules or cells without any collateral damage. Significant benefits of PDT include fewer side effects, much reduced long-term morbidity, high effectiveness, increased selectivity, lower cost, and minimal invasiveness [15][16][17][18]. Notably, site-specific activation of the photosensitizers at the targeted lesion site is the critical factor in PDT.…”