Engineering tumor-specific catalytic nanosystem for NIR-II photothermal-augmented and synergistic starvation/chemodynamic nanotherapy
Abstract Background As an emerging therapeutic modality, chemodynamic therapy (CDT), converting hydrogen peroxide (H2O2) into highly toxic reactive oxygen species (ROS), has been developed for tumor-specific therapy. However, the deficiency of endogenous H2O2 and high concentration of glutathione (G...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Association for the Advancement of Science (AAAS)
2022-11-01
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| Series: | Biomaterials Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40824-022-00317-y |
| _version_ | 1797285763140812800 |
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| author | Shuixiu Zhou Jiahuan Xu Yanfei Dai Yan Wei Liang Chen Wei Feng Yu Chen Xuejun Ni |
| author_facet | Shuixiu Zhou Jiahuan Xu Yanfei Dai Yan Wei Liang Chen Wei Feng Yu Chen Xuejun Ni |
| author_sort | Shuixiu Zhou |
| collection | DOAJ |
| description | Abstract Background As an emerging therapeutic modality, chemodynamic therapy (CDT), converting hydrogen peroxide (H2O2) into highly toxic reactive oxygen species (ROS), has been developed for tumor-specific therapy. However, the deficiency of endogenous H2O2 and high concentration of glutathione (GSH) in the tumor microenvironment (TME) weaken the CDT-based tumor-therapeutic efficacy. Herein, a photothermal-enhanced tumor-specific cascade catalytic nanosystem has been constructed on the basis of glucose oxidase (GOD)-functionalized molybdenum (Mo)-based polyoxometalate (POM) nanoclusters, termed as GOD@POMs. Methods GOD@POMs were synthesized by a facile one-pot procedure and covalently conjugation. Then, its structure was characterized by scanning electron microscope (SEM), transmission electron microscope (TEM), Fourier transform infrared (FTIR) spectroscopy and X-ray photoelectron spectroscopy (XPS). In addition, ultraviolet-visible-near-infrared (UV-vis-NIR) absorption spectrum and infrared thermal camera were applied to evaluate the catalytic and photothermal performance, respectively. Moreover, to confirm the therapeutic effects in vitro, cell counting kit-8 (CCK-8) assay, live/dead staining and ROS staining were performed. Furthermore, the biosafety of GOD@POMs was investigated via blood routine, blood biochemistry and hematoxylin and eosin (H&E) staining in Kunming mice. Besides, the C6 glioma tumor-bearing mice were constructed to evaluate its anti-tumor effects in vivo and its photoacoustic (PA) imaging capability. Notably, RNA sequencing, H&E, TdT-mediated dUTP nick end labeling (TUNEL) and Ki-67 staining were also conducted to disclose its underlying anti-tumor mechanism. Results In this multifunctional nanosystem, GOD can effectively catalyze the oxidation of intratumoral glucose into gluconic acid and H2O2, achieving the cancer starvation therapy. Meanwhile, the generated gluconic acid decreases the pH in TME resulting in POM aggregation, which enables PA imaging-guided tumor-specific photothermal therapy (PTT), especially in the second near-infrared (NIR-II) biological window. Importantly, the Mo (VI) sites on POM can be reduced to Mo (V) active sites in accompany with GSH depletion, and then the post-produced Mo (V) transforms in situ overproduced H2O2 into singlet oxygen (1O2) via Russell mechanism, achieving self-enhanced CDT. Moreover, the PTT-triggered local tumor temperature elevation augments the synergistic nanocatalytic-therapeutic efficacy. Conclusions Consequently, the integration of GOD-induced starvation therapy, H2O2 self-supply/GSH-depletion enhanced Mo-based CDT, and POM aggregation-mediated PTT endow the GOD@POMs with remarkable synergistic anticancer outcomes with neglectable adverse effects. |
| first_indexed | 2024-03-07T18:08:02Z |
| format | Article |
| id | doaj.art-da0599ecaefe46b08b9f6029754a84f3 |
| institution | Directory Open Access Journal |
| issn | 2055-7124 |
| language | English |
| last_indexed | 2024-03-07T18:08:02Z |
| publishDate | 2022-11-01 |
| publisher | American Association for the Advancement of Science (AAAS) |
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| series | Biomaterials Research |
| spelling | doaj.art-da0599ecaefe46b08b9f6029754a84f32024-03-02T08:24:58ZengAmerican Association for the Advancement of Science (AAAS)Biomaterials Research2055-71242022-11-0126111510.1186/s40824-022-00317-yEngineering tumor-specific catalytic nanosystem for NIR-II photothermal-augmented and synergistic starvation/chemodynamic nanotherapyShuixiu Zhou0Jiahuan Xu1Yanfei Dai2Yan Wei3Liang Chen4Wei Feng5Yu Chen6Xuejun Ni7Department of Medical Ultrasound, Affiliated Hospital of Nantong UniversityDepartment of Medical Ultrasound, Affiliated Hospital of Nantong UniversityRadiology Department, Branch of Affiliated Hospital of Nantong UniversityDepartment of Medical Ultrasound, Affiliated Hospital of Nantong UniversityMaterdicine Lab, School of Life Sciences, Shanghai UniversityMaterdicine Lab, School of Life Sciences, Shanghai UniversityMaterdicine Lab, School of Life Sciences, Shanghai UniversityDepartment of Medical Ultrasound, Affiliated Hospital of Nantong UniversityAbstract Background As an emerging therapeutic modality, chemodynamic therapy (CDT), converting hydrogen peroxide (H2O2) into highly toxic reactive oxygen species (ROS), has been developed for tumor-specific therapy. However, the deficiency of endogenous H2O2 and high concentration of glutathione (GSH) in the tumor microenvironment (TME) weaken the CDT-based tumor-therapeutic efficacy. Herein, a photothermal-enhanced tumor-specific cascade catalytic nanosystem has been constructed on the basis of glucose oxidase (GOD)-functionalized molybdenum (Mo)-based polyoxometalate (POM) nanoclusters, termed as GOD@POMs. Methods GOD@POMs were synthesized by a facile one-pot procedure and covalently conjugation. Then, its structure was characterized by scanning electron microscope (SEM), transmission electron microscope (TEM), Fourier transform infrared (FTIR) spectroscopy and X-ray photoelectron spectroscopy (XPS). In addition, ultraviolet-visible-near-infrared (UV-vis-NIR) absorption spectrum and infrared thermal camera were applied to evaluate the catalytic and photothermal performance, respectively. Moreover, to confirm the therapeutic effects in vitro, cell counting kit-8 (CCK-8) assay, live/dead staining and ROS staining were performed. Furthermore, the biosafety of GOD@POMs was investigated via blood routine, blood biochemistry and hematoxylin and eosin (H&E) staining in Kunming mice. Besides, the C6 glioma tumor-bearing mice were constructed to evaluate its anti-tumor effects in vivo and its photoacoustic (PA) imaging capability. Notably, RNA sequencing, H&E, TdT-mediated dUTP nick end labeling (TUNEL) and Ki-67 staining were also conducted to disclose its underlying anti-tumor mechanism. Results In this multifunctional nanosystem, GOD can effectively catalyze the oxidation of intratumoral glucose into gluconic acid and H2O2, achieving the cancer starvation therapy. Meanwhile, the generated gluconic acid decreases the pH in TME resulting in POM aggregation, which enables PA imaging-guided tumor-specific photothermal therapy (PTT), especially in the second near-infrared (NIR-II) biological window. Importantly, the Mo (VI) sites on POM can be reduced to Mo (V) active sites in accompany with GSH depletion, and then the post-produced Mo (V) transforms in situ overproduced H2O2 into singlet oxygen (1O2) via Russell mechanism, achieving self-enhanced CDT. Moreover, the PTT-triggered local tumor temperature elevation augments the synergistic nanocatalytic-therapeutic efficacy. Conclusions Consequently, the integration of GOD-induced starvation therapy, H2O2 self-supply/GSH-depletion enhanced Mo-based CDT, and POM aggregation-mediated PTT endow the GOD@POMs with remarkable synergistic anticancer outcomes with neglectable adverse effects.https://doi.org/10.1186/s40824-022-00317-yPolyoxometalatePhotothermal therapyChemodynamic therapyGlucose oxidaseStarvation therapy |
| spellingShingle | Shuixiu Zhou Jiahuan Xu Yanfei Dai Yan Wei Liang Chen Wei Feng Yu Chen Xuejun Ni Engineering tumor-specific catalytic nanosystem for NIR-II photothermal-augmented and synergistic starvation/chemodynamic nanotherapy Biomaterials Research Polyoxometalate Photothermal therapy Chemodynamic therapy Glucose oxidase Starvation therapy |
| title | Engineering tumor-specific catalytic nanosystem for NIR-II photothermal-augmented and synergistic starvation/chemodynamic nanotherapy |
| title_full | Engineering tumor-specific catalytic nanosystem for NIR-II photothermal-augmented and synergistic starvation/chemodynamic nanotherapy |
| title_fullStr | Engineering tumor-specific catalytic nanosystem for NIR-II photothermal-augmented and synergistic starvation/chemodynamic nanotherapy |
| title_full_unstemmed | Engineering tumor-specific catalytic nanosystem for NIR-II photothermal-augmented and synergistic starvation/chemodynamic nanotherapy |
| title_short | Engineering tumor-specific catalytic nanosystem for NIR-II photothermal-augmented and synergistic starvation/chemodynamic nanotherapy |
| title_sort | engineering tumor specific catalytic nanosystem for nir ii photothermal augmented and synergistic starvation chemodynamic nanotherapy |
| topic | Polyoxometalate Photothermal therapy Chemodynamic therapy Glucose oxidase Starvation therapy |
| url | https://doi.org/10.1186/s40824-022-00317-y |
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