Graphical Abstract
![](https://wqketang.oss-cn-beijing.aliyuncs.com/unzip/large-zip/zip-a02a13d0-2dcb-4736-beb2-ef37c6d67f5b/6342/files/6342-TOC.jpg?Expires=1725756903&OSSAccessKeyId=STS.NSssK71aLjDMY9SbRgGRGskMT&Signature=35F3iK3sfeyHbeuSLnOilRhKNQ8%3D&security-token=CAISywJ1q6Ft5B2yfSjIr5DGOPGD3L5t3YamWx%2FihlIyS91rnK7mtjz2IHtKenhsBOsbtfk1mG5W5%2FgZlqJ9SptIAEfJa9d99Myjb%2F9FltCT1fau5Jko1beHewHKeTOZsebWZ%2BLmNqC%2FHt6md1HDkAJq3LL%2Bbk%2FMdle5MJqP%2B%2FUFB5ZtKWveVzddA8pMLQZPsdITMWCrVcygKRn3mGHdfiEK00he8TouufTinpHMskGA1Aell7Mvyt6vcsT%2BXa5FJ4xiVtq55utye5fa3TRYgxowr%2Fwo0v0YpGya5YzHXwcPskvdKZbo78UqLQlla6w%2BGqFJqvPxr%2Fp8t%2Fx5fWJKAezhVgs8cVM8JOjIqKOscIsixo262SmqFV55c8Fdm%2BgUooJVgIMhTnduUfAPJAGOxzJitP%2BUVGGphr60TEnBL4rB5MUctfzRpwT64j3UTzDnGoABhFRSspTLrn9GrEN9pQYzC6eepGdfWDQh3fr5hA1VnwVUJMCz%2BNQEDWKceF%2FnEjWVMtfbvqYxuyhSCmIMMyh5bEREEKEiD%2BFVv4ZfsqnV7hQy5w6HhIkN8kZzP6L0zPvPgkBLOtdMDeDxhf8dVPrCSG4etXHjxcwUaRVb3ZR7Yu8gAA%3D%3D)
Discover the SciOpen Platform and Achieve Your Research Goals with Ease.
Circulating tumor cells (CTCs) are important biomarkers in the development and progression of lung cancer because they can reach other organs through the blood circulation and form distant metastases, exacerbating lung cancer progression. The presence of CTCs is also the main reason for the failure of nanomedicine-based lung cancer treatments. Therefore, magnetic MoSe2 nanosheets loaded with programmed death-ligand 1 (PD-L1), named PD-L1-MFP NS, were employed here to precisely capture lung cancer CTCs in the blood circulation through the tumor-targeting effect of PD-L1 killing CTCs with highly effective photothermal therapy (PTT). In addition, by increasing the expression of cytomegalovirus UL16-binding protein (ULBP) ligands on tumor cells, the PD-L1-MFP NS further activated natural killer (NK) cells and triggered NK cell-induced cancer immunotherapy, thereby enhancing the overall tumor-killing effect. In summary, this material designed to capture CTCs provides a substantial advancement for personalized PTT-triggered immunotherapy and has great clinical translational potential.
Lin, D. F.; Shen, L. S.; Luo, M.; Zhang, K.; Li, J. F.; Yang, Q.; Zhu, F. F.; Zhou, D.; Zheng, S.; Chen, Y. D. et al. Circulating tumor cells: Biology and clinical significance. Signal Transduct. Target. Ther. 2021, 6, 404.
Tayoun, T.; Faugeroux, V.; Oulhen, M.; Aberlenc, A.; Pawlikowska, P.; Farace, F. CTC-derived models: A window into the seeding capacity of circulating tumor cells (CTCs). Cells 2019, 8, 1145.
Nicolazzo, C.; Raimondi, C.; Mancini, M.; Caponnetto, S.; Gradilone, A.; Gandini, O.; Mastromartino, M.; del Bene, G.; Prete, A.; Longo, F. et al. Monitoring PD-L1 positive circulating tumor cells in non-small cell lung cancer patients treated with the PD-1 inhibitor Nivolumab. Sci. Rep. 2016, 6, 31726.
Yoo, C. E.; Park, J. M.; Moon, H. S.; Joung, J. G.; Son, D. S.; Jeon, H. J.; Kim, Y. J.; Han, K. Y.; Sun, J. M.; Park, K. et al. Vertical magnetic separation of circulating tumor cells for somatic genomic-alteration analysis in lung cancer patients. Sci. Rep. 2016, 6, 37392.
Yoon, H. J.; Kim, T. H.; Zhang, Z.; Azizi, E.; Pham, T. M.; Paoletti, C.; Lin, J.; Ramnath, N.; Wicha, M. S.; Hayes, D. F. et al. Sensitive capture of circulating tumour cells by functionalized graphene oxide nanosheets. Nat. Nanotechnol. 2013, 8, 735–741.
Sinkala, E.; Sollier-Christen, E.; Renier, C.; Rosàs-Canyelles, E.; Che, J.; Heirich, K.; Duncombe, T. A.; Vlassakis, J.; Yamauchi, K. A.; Huang, H. Y. et al. Profiling protein expression in circulating tumour cells using microfluidic western blotting. Nat. Commun. 2017, 8, 14622.
Cai, Y.; Karmakar, B.; Babalghith, A. O.; Batiha, G. E. S.; AlSalem, H. S.; El-Kott, A. F.; Shati, A. A.; Alfaifi, M. Y.; Elbehairi, S. E. I. Decorated Au NPs on lignin coated magnetic nanoparticles: Investigation of its catalytic application in the reduction of aromatic nitro compounds and its performance against human lung cancer. Int. J. Biol. Macromol. 2022, 223, 1067–1082.
Wang, Y.; Zhang, F.; Lin, H. M.; Qu, F. Y. Biodegradable hollow MoSe2/Fe3O4 nanospheres as the photodynamic therapy-enhanced agent for multimode CT/MR/IR imaging and synergistic antitumor therapy. ACS Appl. Mater. Interfaces 2019, 11, 43964–43975.
Chan, L.; Gao, P.; Zhou, W. H.; Mei, C. M.; Huang, Y. Y.; Yu, X. F.; Chu, P. K.; Chen, T. F. Sequentially triggered delivery system of black phosphorus quantum dots with surface charge-switching ability for precise tumor radiosensitization. ACS Nano 2018, 12, 12401–12415.
Irvine, D. J.; Dane, E. L. Enhancing cancer immunotherapy with nanomedicine. Nat. Rev. Immunol. 2020, 20, 321–334.
Myung, J. H.; Park, S. J.; Wang, A. Z.; Hong, S. Integration of biomimicry and nanotechnology for significantly improved detection of circulating tumor cells (CTCs). Adv. Drug Deliv. Rev. 2018, 125, 36–47.
Xu, L. M.; Cheng, C.; Kang, M. L.; Luo, J.; Gong, L. L.; Pang, Q. S.; Wang, J.; Yuan, Z. Y.; Zhao, L. J.; Wang, P. Thoracic radiotherapy (TRT) improved survival in both oligo- and polymetastatic extensive stage small cell lung cancer. Sci. Rep. 2017, 7, 9255.
Emami, F.; Banstola, A.; Vatanara, A.; Lee, S.; Kim, J. O.; Jeong, J. H.; Yook, S. Doxorubicin and anti-PD-L1 antibody conjugated gold nanoparticles for colorectal cancer photochemotherapy. Mol. Pharm. 2019, 16, 1184–1199.
Suresh, K.; Naidoo, J.; Lin, C. T.; Danoff, S. Immune checkpoint immunotherapy for non-small cell lung cancer: Benefits and pulmonary toxicities. Chest 2018, 154, 1416–1423.
Yi, X. Q.; Dai, J.; Han, Y. Y.; Xu, M.; Zhang, X. J.; Zhen, S. J.; Zhao, Z. J.; Lou, X. D.; Xia, F. A high therapeutic efficacy of polymeric prodrug nano-assembly for a combination of photodynamic therapy and chemotherapy. Commun. Biol. 2018, 1, 202.
Vermesh, O.; Aalipour, A.; Ge, T. J.; Saenz, Y.; Guo, Y.; Alam, I. S.; Park, S. M.; Adelson, C. N.; Mitsutake, Y.; Vilches-Moure, J. et al. An intravascular magnetic wire for the high-throughput retrieval of circulating tumour cells in vivo. Nat. Biomed. Eng 2018, 2, 696–705.
Postow, M. A.; Sidlow, R.; Hellmann, M. D. Immune-related adverse events associated with immune checkpoint blockade. N. Engl. J. Med. 2018, 378, 158–168.
Wang, B.; Xu, X. X.; Li, B.; Wei, Z.; Lu, S.; Li, J. J.; Liu, K.; Zhang, H. J.; Wang, F.; Yang, Y. Protein-based nanocarriers for efficient Etoposide delivery and cancer therapy. Nano Res. 2023, 16, 11216–11220.
Liu, Y.; Crowe, W. N.; Wang, L. L.; Lu, Y.; Petty, W. J.; Habib, A. A.; Zhao, D. W. An inhalable nanoparticulate STING agonist synergizes with radiotherapy to confer long-term control of lung metastases. Nat. Commun. 2019, 10, 5108.
Indini, A.; Rijavec, E.; Grossi, F. Circulating biomarkers of response and toxicity of immunotherapy in advanced non-small cell lung cancer (NSCLC): A comprehensive review. Cancers 2021, 13, 1794.
Ge, M.; Guo, H. Y.; Zong, M.; Chen, Z. X.; Liu, Z.; Lin, H.; Shi, J. L. Bandgap-engineered germanene nanosheets as an efficient photodynamic agent for cancer therapy. Angew. Chem., Int. Ed. 2023, 62, e202215795.
Xue, X. D.; Qu, H. J.; Li, Y. P. Stimuli-responsive crosslinked nanomedicine for cancer treatment. Exploration 2022, 2, 20210134.
Zhao, Y.; Zhang, Z. Z.; Pan, Z.; Liu, Y. Advanced bioactive nanomaterials for biomedical applications. Exploration 2021, 1, 20210089.
Wu, C. Y.; Liu, Z. L.; Chen, Z. X.; Xu, D. L.; Chen, L. S.; Lin, H.; Shi, J. L. A nonferrous ferroptosis-like strategy for antioxidant inhibition-synergized nanocatalytic tumor therapeutics. Sci. Adv. 2021, 7, eabj8833.
Liu, Y.; Crowe, W. N.; Wang, L. L.; Petty, W. J.; Habib, A. A.; Zhao, D. W. Aerosolized immunotherapeutic nanoparticle inhalation potentiates PD-L1 blockade for locally advanced lung cancer. Nano Res. 2023, 16, 5300–5310.
Sung, C.; An, J.; Lee, S.; Park, J.; Lee, K. S.; Kim, I. H.; Han, J. Y.; Park, Y. H.; Kim, J. H.; Kang, E. J. et al. Integrative analysis of risk factors for immune-related adverse events of checkpoint blockade therapy in cancer. Nat. Cancer 2023, 4, 844–859.
Pereira-Veiga, T.; Schneegans, S.; Pantel, K.; Wikman, H. Circulating tumor cell-blood cell crosstalk: Biology and clinical relevance. Cell Rep. 2022, 40, 111298.
Jiang, W. X.; Zhang, Z. Y.; Ye, M. M.; Pan, S. Y.; Huang, G. N.; Chen, T. F.; Zhu, X. Q. Morphology-directed radiosensitization of MoSe2 nanoplatforms for promoting cervical cancer radiotherapy. Nano Today 2022, 46, 101598.
He, L. Z.; Nie, T. Q.; Xia, X. J.; Liu, T.; Huang, Y. Y.; Wang, X. J.; Chen, T. F. Designing bioinspired 2D MoSe2 nanosheet for efficient photothermal-triggered cancer immunotherapy with reprogramming tumor-associated macrophages. Adv. Funct. Mater. 2019, 29, 1901240.
Belaroussi, Y.; Bouteiller, F.; Bellera, C.; Pasquier, D.; Perol, M.; Debieuvre, D.; Filleron, T.; Girard, N.; Schott, R.; Mathoulin-Pélissier, S. et al. Survival outcomes of patients with metastatic non-small cell lung cancer receiving chemotherapy or immunotherapy as first-line in a real-life setting. Sci. Rep. 2023, 13, 9584.
Fan, L. Y.; Wang, W. Z.; Wang, Z. H.; Zhao, M. Z. Gold nanoparticles enhance antibody effect through direct cancer cell cytotoxicity by differential regulation of phagocytosis. Nat. Commun. 2021, 12, 6371.
Singh, R. P.; Sharma, G.; Sonali; Singh, S.; Bharti, S.; Pandey, B. L.; Koch, B.; Muthu, M. S. Chitosan-folate decorated carbon nanotubes for site specific lung cancer delivery. Mater. Sci. Eng.: C 2017, 77, 446–458.
Wang, Y.; Zheng, D. L.; Tan, Q. L.; Wang, M. X.; Gu, L. Q. Nanopore-based detection of circulating microRNAs in lung cancer patients. Nat. Nanotechnol. 2011, 6, 668–674.
Wang, J. D.; Zhang, Y. T.; Dong, M.; Liu, Z. P.; Guo, B. B.; Zhang, H. P.; Gao, L. M. Capture and release of circulating tumor cells stimulated by pH and NIR irradiation of magnetic Fe3O4@ZIF-8 nanoparticles. Colloid Surf. B: Biointerf. 2023, 224, 113206.
Labib, M.; Wang, Z. J.; Ahmed, S. U.; Mohamadi, R. M.; Duong, B.; Green, B.; Sargent, E. H.; Kelley, S. O. Tracking the expression of therapeutic protein targets in rare cells by antibody-mediated nanoparticle labelling and magnetic sorting. Nat. Biomed. Eng. 2021, 5, 41–52.
Poudineh, M.; Aldridge, P. M.; Ahmed, S.; Green, B. J.; Kermanshah, L.; Nguyen, V.; Tu, C.; Mohamadi, R. M.; Nam, R. K.; Hansen, A. et al. Tracking the dynamics of circulating tumour cell phenotypes using nanoparticle-mediated magnetic ranking. Nat. Nanotechnol. 2017, 12, 274–281.
Chen, P.; Huang, Y. Y.; Hoshino, K.; Zhang, J. X. J. Microscale magnetic field modulation for enhanced capture and distribution of rare circulating tumor cells. Sci. Rep. 2015, 5, 8745.
Dhar, M.; Wong, J.; Che, J.; Matsumoto, M.; Grogan, T.; Elashoff, D.; Garon, E. B.; Goldman, J. W.; Christen, E. S.; Di Carlo, D. et al. Evaluation of PD-L1 expression on vortex-isolated circulating tumor cells in metastatic lung cancer. Sci. Rep. 2018, 8, 2592.
Li, X.; Yong, T. Y.; Wei, Z. H.; Bie, N. N.; Zhang, X. Q.; Zhan, G. T.; Li, J. Y.; Qin, J. Q.; Yu, J. J.; Zhang, B. X. et al. Reversing insufficient photothermal therapy-induced tumor relapse and metastasis by regulating cancer-associated fibroblasts. Nat. Commun. 2022, 13, 2794.
Hu, J. L.; Wang, F. A.; Liu, F.; Sun, W. T.; Jiang, Q. Y.; Liu, Y. H.; Zhao, Y.; Liu, X. Q. Effective nanotherapeutic approach for metastatic breast cancer treatment by supplemental oxygenation and imaging-guided phototherapy. Nano Res. 2020, 13, 1111–1121.
Harrington, W. N.; Novoselova, M. V.; Bratashov, D. N.; Khlebtsov, B. N.; Gorin, D. A.; Galanzha, E. I.; Zharov, V. P. Photoswitchable spasers with a plasmonic core and photoswitchable fluorescent proteins. Sci. Rep. 2019, 9, 12439.
Chen, Q.; Xu, L. G.; Liang, C.; Wang, C.; Peng, R.; Liu, Z. Photothermal therapy with immune-adjuvant nanoparticles together with checkpoint blockade for effective cancer immunotherapy. Nat. Commun. 2016, 7, 13193.
Zou, B. H.; Xiong, Z. S.; He, L. Z.; Chen, T. F. Reversing breast cancer bone metastasis by metal organic framework-capped nanotherapeutics via suppressing osteoclastogenesis. Biomaterials 2022, 285, 121549.
Lei, Z. Y.; Zhu, W. C.; Xu, S. J.; Ding, J.; Wan, J. X.; Wu, P. Y. Hydrophilic MoSe2 nanosheets as effective photothermal therapy agents and their application in smart devices. ACS Appl. Mater. Interfaces 2016, 8, 20900–20908.
Zhu, L. W.; Chan, L.; Wang, J. P.; Chen, M. K.; Cai, F.; Tian, Y.; Ma, L.; Chen, T. F. Selenium-engineered bottom-up-synthesized lanthanide coordination nanoframeworks as efficiency X-ray-responsive radiosensitizers. Nano Res. 2023, 16, 5169–5175.
Tang, G. G.; Chen, W. T.; Wan, X.; Zhang, F. X.; Xu, J. Construction of magnetic Fe3O4 nanoparticles coupled with flower-like MoSe2 nanosheets for efficient adsorptive removal of methylene blue. Colloid Surf. A: Physicochem. Eng. Asp. 2020, 587, 124291.
Ge, M.; Zong, M.; Xu, D.; Chen, Z.; Yang, J.; Yao, H.; Wei, C.; Chen, Y.; Lin, H.; Shi, J. Freestanding germanene nanosheets for rapid degradation and photothermal conversion. Mater. Today Nano 2021, 15, 100119.
Ge, M.; Xu, D. L.; Chen, Z. X.; Wei, C. Y.; Zhang, Y. X.; Yang, C.; Chen, Y.; Lin, H.; Shi, J. L. Magnetostrictive-piezoelectric-triggered nanocatalytic tumor therapy. Nano Lett. 2021, 21, 6764–6772.
Xu, D. L.; Lin, H.; Qiu, W. J.; Ge, M.; Chen, Z. X.; Wu, C. Y.; You, Y. L.; Lu, X. Y.; Wei, C. Y.; Liu, J. J. et al. Hydrogen-bonded silicene nanosheets of engineered bandgap and selective degradability for photodynamic therapy. Biomaterials 2021, 278, 121172.
Du, Y. X.; Zhang, Z. H.; Yang, Y.; Liu, T.; Chen, T. F.; Li, X. L. Highly active selenium nanotherapeutics combined with metformin to achieve synergistic sensitizing effect on NK cells for osteosarcoma therapy. Nanophotonics 2022, 11, 5101–5111.
Liu, T.; Xu, L. G.; He, L. Z.; Zhao, J. F.; Zhang, Z. H.; Chen, Q.; Chen, T. F. Selenium nanoparticles regulates selenoprotein to boost cytokine-induced killer cells-based cancer immunotherapy. Nano Today 2020, 35, 100975.