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

• Published in: Nature communications Vol. 14; no. 1; pp. 6187 - 17
• Main Authors: Ma, Xiaotu, Liang, Xiaolong, Yao, Meinan, Gao, Yu, Luo, Qi, Li, Xiaoda, Yu, Yue, Sun, Yining, Cheng, Miffy H. Y., Chen, Juan, Zheng, Gang, Shi, Jiyun, Wang, Fan
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 04.10.2023; Nature Publishing Group; Nature Portfolio
• Subjects: 13/109; 13/2; 13/31; 13/51; 14/19; 14/34; 59/5; 59/57; 631/154/152; 631/67/1059/485; 64/60; 692/4028/67/1059/485; Chelation; Clinical trials; Drug delivery; Effectiveness; Gadolinium; Humanities and Social Sciences; Hypoxia; Imaging; Immunological memory; Lipids; Metal ions; multidisciplinary; Myoglobins; Radiation therapy; Radiosensitization; Radiosensitizers; Science; Science (multidisciplinary); Single photon emission computed tomography; Tumors
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-023-41782-w

Gadolinium (Gd 3+ )-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 O 2 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 Gd 3+ , the versatile Mb@Gd-NTs can also chelate 177 Lu 3+ (Mb@ 177 Lu/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. Researchers have been working on radiosensitizers to improve radiotherapy efficacy. Here the authors generate gadolinium nanotexaphyrins (Gd-NTs) that self-assemble and further load it with myoglobulin to relieve hypoxia, improve radiosensitization effects of Gd-coordinated Texaphyrin, and suppress tumor recurrence.