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Theranostics 2023; 13(7):2176-2191. doi:10.7150/thno.83753 This issue Cite

Research Paper

NIR-IIb fluorescence-image guided synergistic surgery/starvation/chemodynamic therapy: an innovative treatment paradigm for malignant non-small cell lung cancers

Xuejiao Han^1,2#, Yingtao Zhong^2#, Chao Mi³, Zhiguo He², Jingsi Gu⁴, Xiaoyong Dai⁵, Chenguang Ma³, Chunyan Feng⁵, Huaqing Chen⁵, Zebin Lan², Zhiyong Guo³, Laiqiang Huang⁵, Baozhu Zhang⁶, Bing Guo^2✉, Qingwei Meng^1✉

1. Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin 150081, China. E-mail address: mengqw@hrbmu.edu.cn
2. School of Science, Shenzhen Key Laboratory of Flexible Printed Electronics Technology, Harbin Institute of Technology, Shenzhen 518055, China. E-mail address: guobing2020@hit.edu.cn
3. UTS-SUStech Joint Research Centre for Biomedical Materials and Devices, Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China
4. Education Center and Experiments and Innovations, Harbin Institute of Technology, Shenzhen 518055, China
5. Institute of Biopharmaceutical and Health Engineering, Shenzhen Key Laboratory of Gene and Antibody Therapy, State Key Laboratory of Chemical Oncogenomics, Shenzhen International Graduate School, Tsinghua University, Shenzhen, Guangdong 518055, China
6. Department of Radiation Oncology, People's Hospital of Shenzhen Baoan District, The Second Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong 518100, China
^#These authors contributed equally to this paper.

✉ Corresponding authors: mengqwedu.cn (Q. Meng), guobing2020edu.cn (B. Guo)

Abstract

Background: Currently, the prognosis and survival rate for patients bearing non-small cell lung cancer (NSCLC) is still quite poor, mainly due to lack of efficient theranostic paradigms to exert in time diagnostics and therapeutics.

Methods: Herein, for NSCLC treatment, we offer a customized theranostic paradigm, termed NIR-IIb fluorescence diagnosis and synergistic surgery/starvation/chemodynamic therapeutics, with a newly designed theranostic nanoplatform PEG/MnCuDCNPs@GOx. The nanoplatform is composed of brightly NIR-II emissive downconversion nanoparticles (DCNPs)-core and Mn/Cu-silica shell loaded with glucose oxidase (GOx) to achieve synergistic starvation and chemodynamic therapy (CDT).

Results: It is found that 10% Ce³⁺ doped in the core and 100% Yb³⁺ doped in the middle shell greatly improves the NIR-IIb emission up to even 20.3 times as compared to the core-shell DCNPs without Ce³⁺ doping and middle shell. The bright NIR-IIb emission of the nanoplatform contributes to sensitive margin delineation of early-stage NSCLC (diameter < 1 mm) with a signal-to-background ratio (SBR) of 2.18, and further assists in visualizing drug distribution and guiding surgery/starvation/chemodynamic therapy. Notably, the starvation therapy mediated by GOx-driven oxidation reaction efficiently depletes intratumoral glucose, and supplies H₂O₂ to boost the CDT mediated by the Mn²⁺ and Cu²⁺, which consequently realized a highly effective synergistic treatment for NSCLC.

Conclusion: This research demonstrates an efficient treatment paradigm for NSCLC with NIR-IIb fluorescence diganosis and image-guided synergistic surgery/starvation/chemodynamic therapeutics.

Keywords: downconversion nanoparticles, NIR-II fluorescence imaging, chemodynamic therapy, early tumors, non-small cell lung cancers

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