Monodisperse and Uniform Mesoporous Silicate Nanosensitizers Achieve Low‐Dose X‐Ray‐Induced Deep‐Penetrating Photodynamic Therapy

Sun, Wenjing; Shi, Tianhang; Luo, Li; Chen, Xiaomei; Lv, Peng; Lv, Ying; Zhuang, Yixi; Zhu, Jinjie; Liu, Gang; Chen, Xiaoyuan; Chen, Hongmin

doi:10.1002/adma.201808024

Cited by 117 publications

(109 citation statements)

References 27 publications

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“…A recent publication suggests that suitable metal dopants (Zn, Mn) in silicate act as nanoscintillators (ZSM) and produce visible X-ray luminescence (450-900 nm); [298] this luminescence then stimulates a conjugated PS, Rose Bengal (RB). This ZSM-RB conjugate was conjugated to RGD peptide forming RB-ZSM-RGD that ensures high specific binding to the U87MG cells.…”

Section: Scintillating Inorganic Nanoparticles Combined With Photosenmentioning

confidence: 99%

Mechanisms for Tuning Engineered Nanomaterials to Enhance Radiation Therapy of Cancer

et al. 2020

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Engineered nanomaterials that produce reactive oxygen species on exposure to X‐ and gamma‐rays used in radiation therapy offer promise of novel cancer treatment strategies. Similar to photodynamic therapy but suitable for large and deep tumors, this new approach where nanomaterials acting as sensitizing agents are combined with clinical radiation can be effective at well‐tolerated low radiation doses. Suitably engineered nanomaterials can enhance cancer radiotherapy by increasing the tumor selectivity and decreasing side effects. Additionally, the nanomaterial platform offers therapeutically valuable functionalities, including molecular targeting, drug/gene delivery, and adaptive responses to trigger drug release. The potential of such nanomaterials to be combined with radiotherapy is widely recognized. In order for further breakthroughs to be made, and to facilitate clinical translation, the applicable principles and fundamentals should be articulated. This review focuses on mechanisms underpinning rational nanomaterial design to enhance radiation therapy, the understanding of which will enable novel ways to optimize its therapeutic efficacy. A roadmap for designing nanomaterials with optimized anticancer performance is also shown and the potential clinical significance and future translation are discussed.

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Section: Scintillating Inorganic Nanoparticles Combined With Photosenmentioning

confidence: 99%

Mechanisms for Tuning Engineered Nanomaterials to Enhance Radiation Therapy of Cancer

et al. 2020

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“…Recent proofof-concept studies using nanoscintillator-photosensitizer conjugates demonstrated that this combinatory approach has a strong therapeutic potential in vitro and in vivo. [13][14][15][16][17][18][19][20][21][22][23][24] Biomedical applications of nanoscintillators are currently mostly centered on this concept of radioluminescence-induced PDT. However, factors by which nanoscintillators can augment radiotherapy outcomes also include a potential synergism with radiotherapy [25] and the use of nanoscintillators that emit UV-C photons to expand the amount and types of DNA damage induced during radiotherapy.…”

Section: Introductionmentioning

confidence: 99%

Radiation Dose‐Enhancement Is a Potent Radiotherapeutic Effect of Rare‐Earth Composite Nanoscintillators in Preclinical Models of Glioblastoma

et al. 2020

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To improve the prognosis of glioblastoma, innovative radiotherapy regimens are required to augment the effect of tolerable radiation doses while sparing surrounding tissues. In this context, nanoscintillators are emerging radiotherapeutics that down-convert X-rays into photons with energies ranging from UV to near-infrared. During radiotherapy, these scintillating properties amplify radiation-induced damage by UV-C emission or photodynamic effects. Additionally, nanoscintillators that contain high-Z elements are likely to induce another, currently unexplored effect: radiation dose-enhancement. This phenomenon stems from a higher photoelectric absorption of orthovoltage X-rays by high-Z elements compared to tissues, resulting in increased production of tissue-damaging photo-and Auger electrons. In this study, Geant4 simulations reveal that rare-earth composite LaF 3 :Ce nanoscintillators effectively generate photo-and Auger-electrons upon orthovoltage X-rays. 3D spatially resolved X-ray fluorescence microtomography shows that LaF 3 :Ce highly concentrates in microtumors and enhances radiotherapy in an X-ray energy-dependent manner. In an aggressive syngeneic model of orthotopic glioblastoma, intracerebral injection of LaF 3 :Ce is well tolerated and achieves complete tumor remission in 15% of the subjects receiving monochromatic synchrotron radiotherapy. This study provides unequivocal evidence for radiation dose-enhancement by nanoscintillators, eliciting a prominent radiotherapeutic effect. Altogether, nanoscintillators have invaluable properties for enhancing the focal damage of radiotherapy in glioblastoma and other radioresistant cancers.

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“…The mesoporous zinc gallogermanates, that is, Zn 3 Ga 2 GeO 8 :Cr 3+ , Yb 3+ , Er 3+ (mZGGOs), were synthesized using a silica templating method as previously described by us. [ 17 ] The as‐prepared mZGGOs displayed typical spherical structures that were monodisperse with uniform size (100.3 ± 10.6 nm) ( Figure a). Clear pore structures were observed in the high‐resolution transmission electron microscopy (HR‐TEM) image (Figure 1b), and nitrogen adsorption isotherm confirmed the formation of pores with a high surface area (Figure 1c).…”

Section: Resultsmentioning

confidence: 99%

X‐Ray‐Induced Persistent Luminescence Promotes Ultrasensitive Imaging and Effective Inhibition of Orthotopic Hepatic Tumors

Shi

Sun

Qin

et al. 2020

Adv Funct Materials

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Persistent luminescence imaging is accompanied by continuous illumination after the removal of excitation light, which can successfully prevent the generation of autofluorescence. In this study, a mesoporous silica template method is used to prepare uniform and monodisperse porous nanophosphors that can generate X‐ray‐excited persistent luminescence (XEPL). By loading photosensitizers, XEPL effectively excites the photosensitizers to produce reactive oxygen species for killing cancer cells. Imaging of orthotopic hepatic tumors in vivo shows that nanophosphors accumulate in the liver tumors through a passive targeting mechanism, as confirmed by the co‐imaging of bioluminescence and X‐ray‐excited luminescence. Under image‐guidance, X‐ray‐induced photodynamic therapy effectively inhibits the growth of orthotopic hepatic tumors with negligible side effects. Overall, X‐ray‐induced persistent luminescence promotes ultrasensitive imaging and effective inhibition of orthotopic hepatic tumors.

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Monodisperse and Uniform Mesoporous Silicate Nanosensitizers Achieve Low‐Dose X‐Ray‐Induced Deep‐Penetrating Photodynamic Therapy

Cited by 117 publications

References 27 publications

Mechanisms for Tuning Engineered Nanomaterials to Enhance Radiation Therapy of Cancer

Mechanisms for Tuning Engineered Nanomaterials to Enhance Radiation Therapy of Cancer

Radiation Dose‐Enhancement Is a Potent Radiotherapeutic Effect of Rare‐Earth Composite Nanoscintillators in Preclinical Models of Glioblastoma

X‐Ray‐Induced Persistent Luminescence Promotes Ultrasensitive Imaging and Effective Inhibition of Orthotopic Hepatic Tumors

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