Myoglobin-loaded gadolinium nanotexaphyrins for oxygen synergy and imaging-guided radiosensitization therapy

Xiaotu Ma, Xiaolong Liang, Meinan Yao, Yu Gao, Qi Luo, Xiaoda Li, Yue Yu, Yining Sun, Miffy H. Y. Cheng, Juan Chen, Gang Zheng (), Jiyun Shi () and Fan Wang ()
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Xiaotu Ma: Chinese Academy of Sciences
Xiaolong Liang: Peking University Third Hospital
Meinan Yao: Peking University
Yu Gao: Chinese Academy of Sciences
Qi Luo: Guangzhou National Laboratory
Xiaoda Li: Peking University
Yue Yu: Chinese Academy of Sciences
Yining Sun: Chinese Academy of Sciences
Miffy H. Y. Cheng: University Health Network
Juan Chen: University Health Network
Gang Zheng: University Health Network
Jiyun Shi: Chinese Academy of Sciences
Fan Wang: Chinese Academy of Sciences

Nature Communications, 2023, vol. 14, issue 1, 1-17

Abstract: Abstract Gadolinium (Gd3+)-coordinated texaphyrin (Gd-Tex) is a promising radiosensitizer that entered clinical trials, but temporarily fails largely due to insufficient radiosensitization efficacy. Little attention has been given to using nanovesicles to improve its efficacy. Herein, Gd-Tex is transformed into building blocks “Gd-Tex-lipids” to self-assemble nanovesicles called Gd-nanotexaphyrins (Gd-NTs), realizing high density packing of Gd-Tex in a single nanovesicle and achieving high Gd-Tex accumulation in tumors. To elucidate the impact of O2 concentration on Gd-Tex radiosensitization, myoglobin (Mb) is loaded into Gd-NTs (Mb@Gd-NTs), resulting in efficient relief of tumor hypoxia and significant enhancement of Gd-Tex radiosensitization, eventually inducing the obvious long-term antitumor immune memory to inhibit tumor recurrence. In addition to Gd3+, the versatile Mb@Gd-NTs can also chelate 177Lu3+ (Mb@177Lu/Gd-NTs), enabling SPECT/MRI dual-modality imaging for accurately monitoring drug delivery in real-time. This “one-for-all” nanoplatform with the capability of chelating various trivalent metal ions exhibits broad clinical application prospects in imaging-guided radiosensitization therapy.

Date: 2023
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DOI: 10.1038/s41467-023-41782-w

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