Theranostics 2023; 13(3):1042-1058. doi:10.7150/thno.78649 This issue Cite

Research Paper

Low-dose X-ray radiodynamic therapy solely based on gold nanoclusters for efficient treatment of deep hypoxic solid tumors combined with enhanced antitumor immune response

Shengcang Zhu1,2#, Feihong Yan1,2#, Lulu Yang3, Bingyi Li1, Ruxian Xue1,2, Wenwen Yu1,2, Yu Wang1,2, Lu Huang1,2, Lijun Wang3, Rongcheng Han1,2✉, Yuqiang Jiang1,2✉

1. State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
2. University of Chinese Academy of Sciences, Beijing 100049, China.
3. Single-Molecule and Nanobiology Laboratory, Department of Biochemistry and Biophysics, School of Basic Medical Sciences, Peking University, Beijing 100191, China.
#These authors contributed equally to this work.

Citation:
Zhu S, Yan F, Yang L, Li B, Xue R, Yu W, Wang Y, Huang L, Wang L, Han R, Jiang Y. Low-dose X-ray radiodynamic therapy solely based on gold nanoclusters for efficient treatment of deep hypoxic solid tumors combined with enhanced antitumor immune response. Theranostics 2023; 13(3):1042-1058. doi:10.7150/thno.78649. https://www.thno.org/v13p1042.htm
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Abstract

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Background: Radiodynamic therapy (RDT) is an emerging novel anti-cancer treatment based on the generation of cytotoxic reactive oxygen species (ROS) at the lesion site following the interaction between low-dose X-ray and a photosensitizer (PS) drug. For a classical RDT, scintillator nanomaterials loaded with traditional PSs are generally involved to generate singlet oxygen (1O2). However, this scintillator-mediated strategy generally suffers from insufficient energy transfer efficiency and the hypoxic tumor microenvironment, and finally severely impedes the efficacy of RDT.

Methods: Gold nanoclusters were irradiated by low dose of X-ray (called RDT) to investigate the production of ROS, killing efficiency of cell level and living body level, antitumor immune mechanism and biosafety.

Results: A novel dihydrolipoic acid coated gold nanoclusters (AuNC@DHLA) RDT, without additional scintillator or photosensitizer assisted, has been developed. In contrast to scintillator-mediated strategy, AuNC@DHLA can directly absorb the X-ray and exhibit excellent radiodynamic performance. More importantly, the radiodynamic mechanism of AuNC@DHLA involves electron-transfer mode resulting in O2-• and HO•, and excess ROS has been generated even under hypoxic conditions. Highly efficient in vivo treatment of solid tumors had been achieved via only single drug administration and low-dose X-ray radiation. Interestingly, enhanced antitumor immune response was involved, which could be effective against tumor recurrence or metastasis. Negligible systemic toxicity was also observed as a consequence of the ultra-small size of AuNC@DHLA and rapid clearance from body after effective treatment.

Conclusions: Highly efficient in vivo treatment of solid tumors had been achieved, enhanced antitumor immune response and negligible systemic toxicity were observed. Our developed strategy will further promote the cancer therapeutic efficiency under low dose X-ray radiation and hypoxic conditions, and bring hope for clinical cancer treatment.

Keywords: gold nanoclusters, radiodynamic therapy, antitumor immune, solid tumor


Citation styles

APA
Zhu, S., Yan, F., Yang, L., Li, B., Xue, R., Yu, W., Wang, Y., Huang, L., Wang, L., Han, R., Jiang, Y. (2023). Low-dose X-ray radiodynamic therapy solely based on gold nanoclusters for efficient treatment of deep hypoxic solid tumors combined with enhanced antitumor immune response. Theranostics, 13(3), 1042-1058. https://doi.org/10.7150/thno.78649.

ACS
Zhu, S.; Yan, F.; Yang, L.; Li, B.; Xue, R.; Yu, W.; Wang, Y.; Huang, L.; Wang, L.; Han, R.; Jiang, Y. Low-dose X-ray radiodynamic therapy solely based on gold nanoclusters for efficient treatment of deep hypoxic solid tumors combined with enhanced antitumor immune response. Theranostics 2023, 13 (3), 1042-1058. DOI: 10.7150/thno.78649.

NLM
Zhu S, Yan F, Yang L, Li B, Xue R, Yu W, Wang Y, Huang L, Wang L, Han R, Jiang Y. Low-dose X-ray radiodynamic therapy solely based on gold nanoclusters for efficient treatment of deep hypoxic solid tumors combined with enhanced antitumor immune response. Theranostics 2023; 13(3):1042-1058. doi:10.7150/thno.78649. https://www.thno.org/v13p1042.htm

CSE
Zhu S, Yan F, Yang L, Li B, Xue R, Yu W, Wang Y, Huang L, Wang L, Han R, Jiang Y. 2023. Low-dose X-ray radiodynamic therapy solely based on gold nanoclusters for efficient treatment of deep hypoxic solid tumors combined with enhanced antitumor immune response. Theranostics. 13(3):1042-1058.

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