Low-dose X-ray radiotherapy–radiodynamic therapy via nanoscale metal–organic frameworks enhances checkpoint blockade immunotherapy

Lu, Kuangda; He, Chunbai; Guo, Nining; Chan, Cheeling; Ni, Kaiyuan; Lan, Guangxu; Tang, Haidong; Pelizzari, Charles A.; Fu, Yang–Xin; Spiotto, Michael T.; Weichselbaum, Ralph R.; Lin, Wenbin

doi:10.1038/s41551-018-0203-4

Cited by 455 publications

(382 citation statements)

References 62 publications

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“…RT has been extensively utilized for cancer therapy, however, excessive generation of ROS is becoming a main cause for radiation‐induced heart disease. GLSO is widely used as functional food composite with potent antioxidant and anti‐inflammatory activity, but it is compromised by the inherent poor solubility and stability for further application in practical.…”

Section: Resultsmentioning

confidence: 99%

Facile Nanolization Strategy for Therapeutic Ganoderma Lucidum Spore Oil to Achieve Enhanced Protection against Radiation‐Induced Heart Disease

Dai

et al. 2019

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Radiotherapy (RT) has been extensively utilized for clinical cancer therapy, however, excessive generation of reactive oxygen species (ROS) is becoming a main cause for radiation‐induced heart disease (RIHD). Ganoderma lucidum spore oil (GLSO) is a popular functional food composite with potent antioxidant activity, but it is compromised by poor solubility and stability for further application. Therefore, a strategy for rational fabrication of GLSO@P188/PEG400 nanosystem (NS) is demonstrated in this study to realize good water solubility and achieve enhanced protection against RIHD. As expected, GLSO@P188/PEG400 NS can attenuate X‐ray‐induced excessive ROS levels thanks to its enhanced free radical scavenging capability, simultaneously protecting on mitochondria from X‐ray irradiation (IR). Moreover, GLSO@P188/PEG400 NS alleviates DNA damage and promotes self‐repair processes against IR, thus recovering G0/G1 proportion back to normal levels. Furthermore, pre‐ and post‐treated GLSO@P188/PEG400 NS demonstrates potential protection on heart from X‐rays in vivo, as evidenced by attenuating cardiac dysfunction and myocardial fibrosis. Meanwhile, the cell antioxidant capacity (including T‐SOD, MDA, and GSH‐x) stays in balance during this process. This study not only provides a promising strategy for facile nanolization of functional food composites with hydrophobic defects but also sheds light on their cardiac protection and action mechanisms against IR‐induced disease.

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Section: Resultsmentioning

confidence: 99%

Facile Nanolization Strategy for Therapeutic Ganoderma Lucidum Spore Oil to Achieve Enhanced Protection against Radiation‐Induced Heart Disease

Dai

et al. 2019

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“…Thus, MOF‐mediated low‐dose radiotherapy combined with anti‐PD‐L1 treatment displayed an abscopal effect in metastatic sites. Last, the same group showed that nanoscale MOF‐mediated radiodynamic therapy can be achieved by low‐dose X‐ray radiotherapy to provide a combination of radiotherapy and radiodynamic‐therapy . When combined with checkpoint blockades, the irradiated nanoscale MOFs not only eliminated local tumors, but also provided durable abscopal responses on distal tumors.…”

Section: Nanoscale Materials For Immunotherapymentioning

confidence: 99%

Materials for Immunotherapy

et al. 2019

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Breakthroughs in materials engineering have accelerated the progress of immunotherapy in preclinical studies. The interplay of chemistry and materials has resulted in improved loading, targeting, and release of immunomodulatory agents. An overview of the materials that are used to enable or improve the success of immunotherapies in preclinical studies is presented, from immunosuppressive to proinflammatory strategies, with particular emphasis on technologies poised for clinical translation. The materials are organized based on their characteristic length scale, whereby the enabling feature of each technology is organized by the structure of that material. For example, the mechanisms by which i) nanoscale materials can improve targeting and infiltration of immunomodulatory payloads into tissues and cells, ii) microscale materials can facilitate cell‐mediated transport and serve as artificial antigen‐presenting cells, and iii) macroscale materials can form the basis of artificial microenvironments to promote cell infiltration and reprogramming are discussed. As a step toward establishing a set of design rules for future immunotherapies, materials that intrinsically activate or suppress the immune system are reviewed. Finally, a brief outlook on the trajectory of these systems and how they may be improved to address unsolved challenges in cancer, infectious diseases, and autoimmunity is presented.

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“…AZr 12 -type MOF,Zr 12 -Ir,was subsequently synthesized by asolvothermal reaction between ZrCl 4 and mixed ligands of H 2 DBB and H 2 L in N,N-dimethylformamide (DMF) at 80 8 8Cu sing acetic acid as the modulator. [7] Postsynthetic metalation of Zr 12 -Ir with NiCl 2 ·6 H 2 O afforded Zr 12 -Ir-Ni whose PXRD pattern and TEM image were unchanged from Zr 12 -Ir (Figure 2c,d). High-resolution TEM (HRTEM) imaging and fast Fourier transform (FFT) of Zr 12 -Ir nanoplates revealed asixfold symmetry (Figure 2b), consistent with the projection of the Zr 12 -Ir structure in the (001) direction.…”

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confidence: 57%

Merging Photoredox and Organometallic Catalysts in a Metal–Organic Framework Significantly Boosts Photocatalytic Activities

et al. 2018

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Metal-organic frameworks (MOFs) have been extensively used for single-site catalysis and light harvesting, but their application in multicomponent photocatalysis is unexplored. We report here the successful incorporation of an Ir photoredox catalyst and a Ni cross-coupling catalyst into a stable Zr MOF, Zr -Ir-Ni, to efficiently catalyze C-S bond formation between various aryl iodides and thiols. The proximity of the Ir and Ni catalytic components to each other (ca. 0.6 nm) in Zr -Ir-Ni greatly facilitates electron and thiol radical transfers from Ir to Ni centers to reach a turnover number of 38 500, an order of magnitude higher than that of its homogeneous counterpart. This work highlights the opportunity in merging photoredox and organometallic catalysts in MOFs to effect challenging organic transformations.

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Low-dose X-ray radiotherapy–radiodynamic therapy via nanoscale metal–organic frameworks enhances checkpoint blockade immunotherapy

Cited by 455 publications

References 62 publications

Facile Nanolization Strategy for Therapeutic Ganoderma Lucidum Spore Oil to Achieve Enhanced Protection against Radiation‐Induced Heart Disease

Facile Nanolization Strategy for Therapeutic Ganoderma Lucidum Spore Oil to Achieve Enhanced Protection against Radiation‐Induced Heart Disease

Materials for Immunotherapy

Merging Photoredox and Organometallic Catalysts in a Metal–Organic Framework Significantly Boosts Photocatalytic Activities

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