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Nanoparticles to mediate X‐ray‐induced photodynamic therapy and Cherenkov radiation photodynamic therapy

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Photodynamic therapy (PDT) has emerged as an attractive option for cancer treatment. However, conventional PDT is activated by light that has poor tissue penetration depths, limiting its applicability in the clinic. Recently the idea of using X‐ray sources to activate PDT and overcome the shallow penetration issue has garnered significant interest. This can be achieved by external beam irradiation and using a nanoparticle scintillator as transducer. Alternatively, research on exploiting Cherenkov radiation from radioisotopes to activate PDT has also begun to flourish. In either approach, the most auspicious success is achieved using nanoparticles as either a scintillator or a photosensitizer to mediate energy transfer and radical production. Both X‐ray induced PDT (X‐PDT) and Cherenkov radiation PDT (CR‐PDT) contain a significant radiation therapy (RT) component and are essentially PDT and RT combination. Unlike the conventional combination, however, in X‐PDT and CR‐PDT, one energy source simultaneously activates both processes, making the combination always in synchronism and the synergy potential maximized. While still in early stage of development, X‐PDT and CR‐PDT address important issues in the clinic and hold great potential in translation. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease
Schematic illustration for X‐PDT and CR‐PDT. Left: Classic X‐PDT. X‐rays excite a nanoscintillator to generate X‐ray luminescence, which in turn activate a photosensitizer to produce cytotoxic ROS. Right: Cherenkov radiation PDT. Cherenkov radiation from radioisotopes is harnessed to activate a photosensitizer to initiate PDT
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(a) Schematic for Cherenkov radiation. (b) Chenekov X‐PDT particle [89Zr]HMSN‐Ce6 schematic, (c) in vivo therapy results with [89Zr]HMSN‐Ce6. (d) Cherenkov X‐PDT with a co‐localization approach using 2‐deoxy‐2′‐(18F)fluoro‐D‐glucose and TiO2‐Tf‐Tc nanoparticles. (e) Co‐localization in vivo therapy results. (Reprinted with permission from Shaffer et al. (), Kamkaew et al. () and Kotagiri et al. (). Copyright 2017, 2016 and 2018 American Chemical Society and Nature Publishing Group)
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(a) The emission spectrum (red) of CdS nanoparticles and the absorption spectrum (black) of tretrakis (o‐aminophenyl) porphyrin (TOAP). (b) Fluorescence emission spectra of TOAP (black), CdS nanoparticles (green), and TOAP‐CdS nanoparticle conjugates (red) (Reprinted with permission from W. Chen and Zhang (). Copyright 2006 American Scientific Publishers)
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Silica nanowire based X‐PDT. (a) Schematic of the SiC/SiOx/H2TPACPP system. Grown nanowires are functionalized with azide groups; the H2TCPP porphyrin derivative containing an alkyne group (H2TPACPP) is synthesized by converting the carboxy groups into N‐propynylamides; the nanohybrid is constructed by bonding H2TPACPP to the NWs. (b) Left: SEM image of the as‐grown nanowire network on Si substrate. Right: TEM image of two neighbor nanowires. (c) TEM of cellular uptake and internalization of the nanowires during the first 24 hr. (d) Fluorescence spectra acquired at room temperature over as‐grown nanowires. (e) 1O2 generated, as a function of the radiation dose. (f) Histogram of clongenic survival assay. (Reprinted with permission from Rossi et al. (). Copyright 2015 Nature Publishing Group)
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Nanoscale metal organic layers for X‐PDT. (a) Schematic for Hf‐based nMOL X‐PDT agent. (b) Photosensitizers. Top: Ir[2,2′‐bipyridine(2‐phenylpyridine)2]+. Bottom: [Ru(2,2′‐bipyridine)3]2+ c) physical characterization. Top left: TEM nMOL bottom left: HRTEM image, inset: FFT pattern. Top right: Tapping‐mode AFM topography. Bottom right: Height profile along the white line. d) SOSG assay results. Samples were treated by 225 kVp irradiation. (e) in vivo therapeutic effect of nMOL (left:CT26, right:MC38). (Reprinted with permission from Lan et al. (). Copyright 2017 John Wiley and Sons)
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X‐PDT with strontium aluminum oxide (SAO) nanoparticles. (a) Schematic illustration of the working mechanism. A SAO nanoparticle core is coated with two layers of silica. MC540, a photosensitizer of matching, is loaded into the mesoporous layer. (b) TEM image of [email protected]2 nanoparticles. (c) Comparison between the XEOL of SAO (red) and the absorbance of MC540 (black). (d) MTT assays showing that SAO nanoparticle‐mediated X‐PDT efficiently killed U87MG cells. (e) Western blotting assays. In the presence of SAO nanoparticles, radiation‐induced cellular damage is shifted from DNA breaks to lipid peroxidation. (f) in vivo X‐PDT therapy results. (Reprinted with permission from Hongmin Chen et al., () and G. D. Wang et al., (). Copyright 2015 and 2016 American Chemical Society)
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