ADVANCED MATERIALS
·
2025
·
IF 26.8
Ruru Zhang,Mei Chen,Hui Zhou,Yan Liu,Yi Wang,Can Chen,Yueping Li,Jianfeng Zeng,Jiabin Cui,Ruixue Duan,Mingyuan Gao
Radiotherapy (RT) hinges on DNA damage-induced cancer cell death and the subsequent anti-tumor immunity. However, the efficacy of RT is curtailed by cell cycle heterogeneity and an immunosuppressive tumor microenvironment, which foster radioresistance. Here an ion generator-based RT enhancement strategy is demonstrated in a mouse model of the radioresistant tumor. The ion generator is degraded in the tumor microenvironment, resulting in iron-triggered ferroptosis that enhanced immunogenic cell death and a manganese-activated stimulator of interferon gene that reversed the immunosuppressive environment. As a result, the proposed strategy promotes dendritic cells maturity, augmentes CD8 + T cell infiltration of tumors, suppresses intratumoral myeloid-derived suppressor cells, and limits the M2 macrophages polarization, indicating the formation of an immunoreactive microenvironment. Significantly, this approach impedes the growth of not just primary, but also distal metastatic tumors. It is thus believed that the current ion generator provides a robust and enduring countermeasure to radioresistant cancer and its metastasis, with potential implications for enhancing the efficacy of RT in clinically resistant tumors.
研究领域:
肿瘤学
·
免疫学
·
放射生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2020
·Vol. 8
·期 17
·4739-4749
·
IF 6.183
Zhicheng Zhang,Li Wang,Yawen Ding,Jinhui Wu,Yiqiao Hu,Ahu Yuan
Radiotherapy (RT) is one of the most extensive and effective approaches available for clinical tumor treatment. However, tumor microenvironments including hypoxia and histone deacetylase (HDAC) overexpression could induce radiation resistance, leading to tumor recurrence. Herein, nanoparticles (CAT-SAHA@PLGA) encapsulating catalase and HDAC inhibitor SAHA exhibited protected catalytic activity of catalase and prolonged the pharmacokinetic exposure of the HDAC inhibitor. Overall, the established CAT-SAHA@PLGA nanoparticles could overcome radiation resistance by synergistically increasing tumor oxygenation and inhibiting HDAC activity.
研究领域:
肿瘤学
·
放射生物学
·
纳米技术
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2021
·Vol. 9
·期 6
·1625-1637
·
IF 6.331
Zhenhu He,Haixiong Yan,Wenbin Zeng,Kai Yang,Pengfei Rong
Radiotherapy occupies an essential position in curing and palliating a wide range of solid tumors based on DNA damage responses to eradicate cancer cells. However, the tumor microenvironment generally exhibits the characteristics of hypoxia and glutathione overexpression, which play a critical role in radioresistance, to prevent irreparable breaks to DNA and necrocytosis of cancer cells. Herein, polyethylene glycol (PEG) functionalized manganese ferrite nanoparticles (MnFe2O4-PEG) are designed to enable self-sufficiency of oxygen by continuously catalyzing the decomposition of endogenous hydrogen peroxide. Simultaneously, the nano-platform can consume GSH to reduce the loss of reactive oxygen species in radiotherapy and achieve better therapeutic effects at the cellular and animal levels. In addition, the MnFe2O4-PEG could act as an optimal T1- and T2-weighted contrast medium for tumor-specific magnetic resonance imaging. This work proposes a systematically administered radiosensitizer that can selectively reside in tumor sites via the enhanced permeability and retention effect to relieve hypoxia and reduce GSH concentration, combined with dual-mode magnetic resonance imaging, achieving precise and effective image-guided tumor therapy.
研究领域:
纳米技术
·
放射学
·
肿瘤学
·
生物医学工程
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2018
·
IF 8.806
Ruyi Zhou,Huamei Wang,Yufei Yang,Chenyang Zhang,Xinghua Dong,Jiangfeng Du,Liang Yan,Guangjin Zhang,Zhanjun Gu,Yuliang Zhao
Radioresistance resulted from the intrinsic features of tumors often gives rise to unsatisfied therapeutic outcome. In particular, the tumor microenvironment (TME) with abundant antioxidants, elevated hydrogen peroxide (H 2 O 2 ) and hypoxia has been believed as a tremendous obstacle for radiotherapy . Therefore, developing an effective radiosensitizer in response to both X-ray and the TME is highly imperative but remains a challenge so far. Here, we for the first time explore bismuth heteropolytungstate (BiP 5 W 30 ) nanoclusters as radiosensitizers for the TME-manipulated enhancement of radiotherapy. On the one hand, BiP 5 W 30 nanoclusters can increase radiation dose deposition within tumors by high-Z elements like Bi and W. On the other hand, in virtue of the unique electron structure and multi-electron property, they have the capability of depleting glutathione (GSH) via redox reaction and catalyzing the decomposition of H 2 O 2 to HO to enhance ROS generation upon X-ray radiation. Moreover, reduced graphene oxide (rGO) coupled with BiP 5 W 30 can further improve radiocatalytic activity through promoting electron-hole separation. Simultaneously, due to the considerable near-infrared absorption of rGO, photothermal therapy can overcome the tumor hypoxia microenvironment and thus synergize with radiotherapy. In addition to providing a promising radiosensitizer, this finding is expected to extend the application of polyoxometalates used in the biomedical field .
研究领域:
肿瘤学
·
放射治疗
·
纳米技术
·
生物医学工程
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Small
·
2024
·
IF 13
Chen Jian,Tingting Wu,Lulu Wang,Chen Gao,Zhiwen Fu,Qian Zhang,Chen Shi
Radiation resistance in breast cancer resulting in residual lesions or recurrence is a significant cause to radiotherapy failure. Cancer-associated fibroblasts (CAFs) and radiotherapy-induced senescent CAFs can further lead to radiation resistance and tumor immunosuppressive microenvironment. Here, an engineering cancer-cell-biomimetic nanoplatform is constructed for dual-targeted clearance of CAFs as well as senescent CAFs. The nanoplatform is prepared by 4T1 cell membrane vesicles chimerized with FAP single-chain fragment variable as the biomimetic shell for targeting of CAFs and senescent CAFs, and PLGA nanoparticles (NPs) co-encapsulated with nintedanib and ABT-263 as the core for clearance of CAFs and senescent CAFs, which are noted as FAP-CAR-CM@PLGA-AB NPs. It is evidenced that FAP-CAR-CM@PLGA-AB NPs directly suppressed the tumor-promoting effect of senescent CAFs. It also exhibits prolonged blood circulation and enhanced tumor accumulation, dual-cleared CAFs and senescent CAFs, improved radiation resistance in both acquired and patient-derived radioresistant tumor cells, and effective antitumor effect with the tumor suppression rate of 86.7%. In addition, FAP-CAR-CM@PLGA-AB NPs reverse the tumor immunosuppressive microenvironment and enhance systemic antitumor immunity. The biomimetic system for dual-targeted clearance of CAFs and senescent CAFs provides a potential strategy for enhancing the radio-sensitization of breast cancer.
研究领域:
生物医学工程
·
肿瘤学
·
纳米技术
·
免疫治疗
·
癌症生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2022
·
IF 5.999
Dongdong Li,Jing Zhao,Jun Ma,Huiquan Yang,Xiaodong Zhang,Yuyu Cao,Peidang Liu
Radiotherapy is one of the main treatment modalities for glioma, but the therapeutic efficacy is often limited by the radioresistance of tumor cells. The radiosensitization effects of silver nanoparticles (AgNPs) and gold nanoparticles (AuNPs) on tumors have been confirmed by previous studies. To enhance the specific killing effect of irradiation on tumor cells, targeted modification of radiosensitizers is urgently needed. Herein, we developed polyethylene glycol (PEG)-coated [email protected] core-shell nanoparticles (PSGNPs) modified with GMT8 aptamer (GSGNPs) and evaluated their radiosensitization effects on glioma cells through in vivo and in vitro experiments. Transmission electron microscope image showed that the prepared PSGNPs had a spherical core-shell structure with an average size of 11 nm. The ultraviolet-visible absorption spectra and Fourier transform infrared spectra displayed that GMT8 was successfully conjugated to PSGNPs. The results of dark-field imaging revealed that the targeting ability of GSGNPs to U87 glioma cells was much better than that to normal human microvascular endothelial cells. Additionally, it was also found that the endocytic pathways of GSGNPs mainly involved clathrin-mediated endocytosis and macropinocytosis . The sensitization enhancement ratio of GSGNPs was calculated to be 1.62, which was higher than that of PSGNPs. In vivo imaging results showed that GSGNPs exhibited good tumor targeting and retention capabilities, and the fluorescence intensity ratio of Cy5-GSGNPs to Cy5-PSGNPs reached a peak at 4 h after injection. More importantly, the median survival time of mice bearing U87 glioma was significantly prolonged after intravenous administration of GSGNPs combined with radiotherapy. This work demonstrated that GSGNPs could be used as an effective nano-radiosensitizer for targeted radiotherapy of glioma.
研究领域:
癌症治疗
·
纳米技术
·
放射生物学
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）