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Upconversion mesoporous silica nanoparticles co-delivering celecoxib and rose bengal enable multimodal immunogenic and anti-angiogenic therapy for spinal metastasis of non-small cell lung cancer

Oncogene (2026)Cite this article

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Abstract

Non-small cell lung cancer (NSCLC) with spinal metastasis represents a clinical challenge due to its aggressive nature, limited treatment options, and profound impact on patient quality of life. Here, we report the development of an innovative upconversion mesoporous silica nanoparticle (UCMS) platform co-loaded with celecoxib and rose bengal (UCMS@CXB/RB), engineered to synergistically combine photodynamic therapy (PDT) and cyclooxygenase-2 (COX-2) inhibition. Upon near-infrared (NIR) irradiation, UCMS@CXB/RB generated abundant reactive oxygen species, triggered immunogenic cell death, and significantly suppressed prostaglandin E2 signaling, leading to reduced angiogenesis and improved antitumor immunity. In vitro and in vivo studies confirmed that this nanoplatform effectively remodeled the tumor microenvironment, inhibited tumor growth, and alleviated cancer-induced spinal dysfunction. Single-cell multi-omics analysis further revealed dynamic crosstalk among immune cells, tumor cells, and endothelial populations, providing mechanistic insights into the multifaceted therapeutic effects of UCMS@CXB/RB. Our results underscore the clinical potential of integrating PDT with targeted COX-2 blockade to address the complex pathophysiology of NSCLC spinal metastasis. This study presents a promising minimally invasive therapeutic strategy with strong translational relevance for managing metastatic NSCLC and improving patient outcomes.

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Fig. 1: Preparation and characterization of UCMS@CXB/RB.
Fig. 2: In vitro release, photodynamic effect, and cellular uptake of UCMS@CXB/RB.
Fig. 3: Effect of UCMS@CXB/RB on tumor cell ICD.
Fig. 4: Effect of UCMS@CXB/RB on tumor cell angiogenesis through COX-2 activity.
Fig. 5: Therapeutic effect of UCMS@CXB/RB combined with PDT on LC-SM.
Fig. 6: Effect of UCMS@CXB/RB combined with PDT on immune activation and angiogenesis in LC-SM.
Fig. 7: scRNA-seq data analysis of UCMS@CXB/RB combined with PDT treatment in LC-SM.
Fig. 8: RNA-seq data analysis of UCMS@CXB/RB combined with PDT treatment in LC-SM.

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References

  1. Yu J, Cai W, Zhou T, Men B, Chen S, Tu D, et al. CEACAM1 increased the lymphangiogenesis through miR-423-5p and NF- kB in Non-Small Cell Lung Cancer. Biochem Biophys Rep. 2024;40:101833.

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Gensheimer MF, Kotha NV, Vitzthum LK, Chin AL, Jackson S, van ’t Erve I, et al. A phase 2 single-arm trial of high-dose precision targeted radiation therapy added to immunotherapy for patients with metastatic non-small cell lung cancer. Int J Radiat Oncol Biol Phys. 2025;121:711–9.

    Article  PubMed  Google Scholar 

  3. Wu L, Hu M, Li P, Man Q, Yuan Q, Zhang X, et al. Microwave ablation combined with percutaneous vertebroplasty for treating painful non-small cell lung cancer with spinal metastases under real-time temperature monitoring. J Cancer Res Ther. 2024;20:540–6.

    Article  PubMed  Google Scholar 

  4. Hendriks LEL, Hermans BCM, van den Beuken—van Everdingen MHJ, Hochstenbag MMH, Dingemans A-MC. Effect of bisphosphonates, denosumab, and radioisotopes on bone pain and quality of life in patients with non–small cell lung cancer and bone metastases: a systematic review. J Thorac Oncol. 2016;11:155–73.

    Article  PubMed  Google Scholar 

  5. Uei H, Tokuhashi Y, Maseda M. Analysis of the relationship between the epidural spinal cord compression (ESCC) scale and paralysis caused by metastatic spine tumors. Spine. 2018;43:E448–E455.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Wu L, Wang L, Yang J, Jia W, Xu Y. Clinical features, treatments, and prognosis of intramedullary spinal cord metastases from lung cancer: a case series and systematic review. Neurospine. 2022;19:65–76.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Arrigo RT, Kalanithi P, Cheng I, Alamin T, Carragee EJ, Mindea SA, et al. Predictors of survival after surgical treatment of spinal metastasis. Neurosurgery. 2011;68:674–81.

    Article  PubMed  Google Scholar 

  8. Guckenberger M, Dahele M, Ong WL, Sahgal A. Stereotactic body radiation therapy for spinal metastases: benefits and limitations. Semin Radiat Oncol. 2023;33:159–71.

    Article  PubMed  Google Scholar 

  9. Jaipanya P, Chanplakorn P. Spinal metastasis: narrative reviews of the current evidence and treatment modalities. J Int Med Res. 2022;50. https://doi.org/10.1177/03000605221091665

  10. Harel R, Angelov L. Spine metastases: current treatments and future directions. Eur J Cancer. 2010;46:2696–707.

    Article  PubMed  Google Scholar 

  11. Cai Q. Cancer-associated adipocytes in the ovarian cancer microenvironment. Am J Cancer Res. 2024;14:3259–79.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Zhao Y, Guo S, Deng J, Shen J, Du F, Wu X, et al. VEGF/VEGFR-targeted therapy and immunotherapy in non-small cell lung cancer: targeting the tumor microenvironment. Int J Biol Sci. 2022;18:3845–58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Wang Y, Chen R, Wa Y, Ding S, Yang Y, Liao J, et al. Tumor immune microenvironment and immunotherapy in brain metastasis from non-small cell lung cancer. Front. Immunol. 2022;13. https://doi.org/10.3389/fimmu.2022.829451.

  14. Liu W, Powell CA, Wang Q. Tumor microenvironment in lung cancer-derived brain metastasis. Chin Med J. 2022;135:1781–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Oliveira Santos M de J, Teles-Souza J, de Araújo-Calumby RF, Copeland RL Jr, et al. Advances, limitations and perspectives in the use of celecoxib-loaded nanocarriers in therapeutics of cancer. Discover Nano. 2024;19. https://doi.org/10.1186/s11671-024-04070-0.

  16. Mahboubi-Rabbani M, Abdolghaffari AH, Ghesmati M, Amini A, Zarghi A. Selective COX-2 inhibitors as anticancer agents: a patent review (2018-23). Expert Opin Ther Pat. 2024;34:733–57.

    Article  CAS  PubMed  Google Scholar 

  17. Akl MM, Ahmed A. Cytobiological alterations induced by celecoxib as an anticancer agent for breast and metastatic breast cancer. Adv Pharm Bull. 2024;14:604–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Xi Z, Jiang Y, Ma Z, Li Q, Xi X, Fan C, et al. Using mesoporous silica-based dual biomimetic nano-erythrocytes for an improved antitumor effect. Pharmaceutics. 2023;15:2785.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Xiao, Meng H, Songtao Li X, Li Z, Fang S, Wang Y, et al. Combined drug anti-deep vein thrombosis therapy based on platelet membrane biomimetic targeting nanotechnology. Biomaterials. 2024;311:122670.

    Article  CAS  PubMed  Google Scholar 

  20. Rastegari E, Hsiao Y-J, Lai W-Y, Lai Y-H, Yang T-C, Chen S-J, et al. An update on mesoporous silica nanoparticle applications in nanomedicine. Pharmaceutics. 2021;13:1067.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Lucky SS, Soo KC, Zhang Y. Nanoparticles in photodynamic therapy. Chem Rev. 2015;115:1990–2042.

    Article  CAS  PubMed  Google Scholar 

  22. Mudhakir D, Sadaqa E, Permana Z, Mumtazah JE, Zefrina NF, Xeliem JN, et al. Dual-functionalized mesoporous silica nanoparticles for celecoxib delivery: amine grafting and imidazolyl pei gatekeepers for enhanced loading and controlled release with reduced toxicity. Molecules. 2024;29:3546.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Han C, Zhang S, Huang H, Dong Y, Sui X, Jian B, et al. In vitro and in vivo evaluation of core–shell mesoporous silica as a promising water-insoluble drug delivery system: improving the dissolution rate and bioavailability of celecoxib with needle-like crystallinity. J Pharm Sci. 2019;108:3225–32.

    Article  CAS  PubMed  Google Scholar 

  24. Yu J, Wang Y, Zhou S, Li J, Wang J, Chi D, et al. Remote loading paclitaxel–doxorubicin prodrug into liposomes for cancer combination therapy. Acta Pharm Sin B. 2020;10:1730–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. An J, Lv K-P, Chau CV, Lim JH, Parida R, Huang X, et al. Lutetium texaphyrin–celecoxib conjugate as a potential immuno-photodynamic therapy agent. J Am Chem Soc. 2024;146:19434–48.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Geng Y, Lou J, Wu J, Tao Z, Yang N, Kuang J, et al. NEMO-binding domain/IKKγ inhibitory peptide alleviates neuronal pyroptosis in spinal cord injury by inhibiting ASMase-induced lysosome membrane permeabilization. Adv Sci. 2024;11. https://doi.org/10.1002/advs.202405759.

  27. Ferrario A, Lim S, Xu F, Luna M, Gaffney KJ, Petasis NA, et al. Enhancement of photodynamic therapy by 2,5-dimethyl celecoxib, a non-cyclooxygenase-2 inhibitor analog of celecoxib. Cancer Lett. 2011;304:33–40.

    Article  CAS  PubMed  Google Scholar 

  28. Kong R-J, Li Y-M, Huang J-Q, Yan N, Wu Y-Y, Cheng H. Self-delivery photodynamic re-educator enhanced tumor treatment by inducing immunogenic cell death and improving immunosuppressive microenvironments. ACS Appl Mater Interfaces. 2023;15:59165–74.

    Article  CAS  PubMed  Google Scholar 

  29. Zhang W, Yu B, Chen X, Yan M, Liu Q, Liu Y, et al. Tumor homing chimeric peptide rhomboids to improve photodynamic performance by inhibiting therapy-upregulated cyclooxygenase-2. Small. 2024;20. https://doi.org/10.1002/smll.202309882.

  30. Sun W, Zhou Z, Pratx G, Chen X, Chen H. Nanoscintillator-mediated X-ray induced photodynamic therapy for deep-seated tumors: from concept to biomedical applications. Theranostics. 2020;10:1296–318.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Zhu S, Lin S, Han R. Treating deep-seated tumors with radiodynamic therapy: progress and perspectives. Pharmaceutics. 2024;16:1135.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Li S, Jiang M, Wang L, Yu S. Combined chemotherapy with cyclooxygenase-2 (COX-2) inhibitors in treating human cancers: Recent advancement. Biomedicine &amp. Pharmacotherapy. 2020;129:110389.

    Article  CAS  Google Scholar 

  33. Debucquoy A, Goethals L, Geboes K, Roels S, Mc Bride WH, Haustermans K. Molecular responses of rectal cancer to preoperative chemoradiation. Radiother Oncol. 2006;80:172–7.

    Article  CAS  PubMed  Google Scholar 

  34. Hu J-W, Chen B, Zhang J, Qi Y-P, Liang J-H, Zhong J-H, et al. Novel combination of celecoxib and metformin improves the antitumor effect by inhibiting the growth of Hepatocellular Carcinoma. J Cancer. 2020;11:6437–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Niu G, Bi X, Kang Y, Zhao H, Li R, Ding M, et al. An acceptor–donor–acceptor structured nano-aggregate for nir-triggered interventional photoimmunotherapy of cervical cancer. Adv Mater. 2024;36. https://doi.org/10.1002/adma.202407199.

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Funding

This study was supported by the Revitalizing Liaoning Talents Program-Medical Experts Project (No. YXMJ-JC-10).

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Author notes

  1. These authors contributed equally: Xinxin Li, Shuangmei Liu.

Authors and Affiliations

  1. Dalian Medical University, Dalian, China

    Xinxin Li & Ruoyu Wang

  2. Department of Hematology and Breast Cancer, Cancer Hospital of Dalian University of Technology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang, China

    Xinxin Li

  3. Department of Anesthesiology, Shengjing Hospital of China Medical University, Shenyang, China

    Shuangmei Liu

  4. The Key Laboratory of Biomarker High Throughput Screening and Target Translation of Breast and Gastrointestinal Tumor, Affiliated Zhongshan Hospital of Dalian University, Zhongshan District, Dalian, China

    Ruoyu Wang

  5. Department of Interventional Therapy, The First Hospital of China Medical University, Shenyang, China

    Xinlei Wang

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Contributions

Xinxin Li and Shuangmei Liu contributed equally to this work. Xinxin Li designed and performed most of the experiments, analyzed the data, and drafted the manuscript. Shuangmei Liu assisted with animal studies and photodynamic therapy experiments. Ruoyu Wang supervised the project, provided conceptual guidance, and revised the manuscript. Xinlei Wang contributed to study design, clinical interpretation, and manuscript editing. All authors discussed the results and approved the final version of the manuscript.

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Correspondence to Ruoyu Wang or Xinlei Wang.

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Li, X., Liu, S., Wang, R. et al. Upconversion mesoporous silica nanoparticles co-delivering celecoxib and rose bengal enable multimodal immunogenic and anti-angiogenic therapy for spinal metastasis of non-small cell lung cancer. Oncogene (2026). https://doi.org/10.1038/s41388-026-03679-y

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