TME-targeting theranostic agent uses NIR tracking for tumor diagnosis and surgical resection and acts as chemotherapeutic showing enhanced efficiency and minimal toxicity

Xu, Zhongyuan; Qian, Jianqiang; Meng, Chi; Liu, Yun; Ding, Qian; Wu, Hongmei; Li, Peng; Ran, Fansheng; Liu, Gong-Qing; Wang, Yunyun; Ling, Yong

doi:10.7150/thno.68074

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Nanotheranostics 2024; 8(3): 380-400. [Abstract] [Full text] [PDF]

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Theranostics 2022; 12(6):2535-2548. doi:10.7150/thno.68074 This issue Cite

Research Paper

TME-targeting theranostic agent uses NIR tracking for tumor diagnosis and surgical resection and acts as chemotherapeutic showing enhanced efficiency and minimal toxicity

Zhongyuan Xu^1,#, Jianqiang Qian^1,#, Chi Meng^1,#, Yun Liu¹, Qian Ding¹, Hongmei Wu¹, Peng Li², Fansheng Ran¹, Gong-Qing Liu¹, Yunyun Wang^1,✉, Yong Ling^1,2✉

1. School of Pharmacy and Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong 226001, PR China.
2. The Affiliated Hospital of Nantong University, Nantong University, Nantong 226001, PR China.
^#These three authors contributed equally to this work.

Citation:

Xu Z, Qian J, Meng C, Liu Y, Ding Q, Wu H, Li P, Ran F, Liu GQ, Wang Y, Ling Y. TME-targeting theranostic agent uses NIR tracking for tumor diagnosis and surgical resection and acts as chemotherapeutic showing enhanced efficiency and minimal toxicity. Theranostics 2022; 12(6):2535-2548. doi:10.7150/thno.68074. https://www.thno.org/v12p2535.htm

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Abstract

Rationale: Precise diagnosis and effective therapy of the tumor microenvironment (TME) remains a challenge. Fluorescence tracers for monitoring primary tumors are currently reported; however, they face challenges in accurately delineating tumors in real-time during surgery, including interference from the background and insufficient accumulation of imaging reagents at tumor sites. Additionally, although the natural product podophyllotoxin (PPT) had potent and broad anti-tumor activity, the poor tumor target specificity and high toxicity of PPT extremely limited its clinical application.

Methods: In the current study, a novel theranostic agent PBB was designed and synthesized by coupling the natural chemotherapeutic drug PPT with a near-infrared (NIR) fluorescence probe hemicyanine (CyOH) via redox-responsive thiolactate linker and introducing biotin to CyOH to enhance the active target ability. The activation mechanism of PBB was characterized by absorption spectra, fluorescence spectra, and HPLC. Subsequently, we investigated its imaging action, anti-tumor activity, and toxicity in vitro and in vivo.

Results: In vitro experiments, PBB was verified to possess a ROS/GSH-responsive molecular switch, impelling PBB to release a fluorescent fragment and active drug PPT and selectively lighting up tumor cells but not the normal cells. As such, PBB was demonstrated to selectively inhibit the growth of tumor cells by inducing intracellular accumulation of ROS and MMP depolarization. More importantly, PBB significantly suppressed hepatic tumor growth and minimized the adverse effects caused by PPT, including acute toxicity and impaired liver function. Finally, the NIR fluorescence accumulated in the tumor tissue and stayed continuous for over 24h, and PBB provided precise visualization and highly selective fluorescence diagnosis to guide tumor resection.

Conclusions: Therefore, the multilevel targeting theranostic agent provided a novel tool for precise diagnosis, real-time monitoring, and efficient tumor chemotherapy with high safety.

Keywords: Tumor microenvironment, NIR fluorescence, ROS/GSH -dual-responsive, Podophyllotoxin (PPT), Theranostic agent.

Citation styles

APA

Xu, Z., Qian, J., Meng, C., Liu, Y., Ding, Q., Wu, H., Li, P., Ran, F., Liu, G.Q., Wang, Y., Ling, Y. (2022). TME-targeting theranostic agent uses NIR tracking for tumor diagnosis and surgical resection and acts as chemotherapeutic showing enhanced efficiency and minimal toxicity. Theranostics, 12(6), 2535-2548. https://doi.org/10.7150/thno.68074.

ACS

Xu, Z.; Qian, J.; Meng, C.; Liu, Y.; Ding, Q.; Wu, H.; Li, P.; Ran, F.; Liu, G.Q.; Wang, Y.; Ling, Y. TME-targeting theranostic agent uses NIR tracking for tumor diagnosis and surgical resection and acts as chemotherapeutic showing enhanced efficiency and minimal toxicity. Theranostics 2022, 12 (6), 2535-2548. DOI: 10.7150/thno.68074.

NLM

CSE

Xu Z, Qian J, Meng C, Liu Y, Ding Q, Wu H, Li P, Ran F, Liu GQ, Wang Y, Ling Y. 2022. TME-targeting theranostic agent uses NIR tracking for tumor diagnosis and surgical resection and acts as chemotherapeutic showing enhanced efficiency and minimal toxicity. Theranostics. 12(6):2535-2548.

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