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<p>Non-small cell lung cancer (NSCLC) remains one of the most lethal malignancies worldwide, highlighting the urgent need for the development of novel multifunctional therapeutic strategies. In this study, a bioinspired nanocomposite drug delivery system was designed and constructed by covalently modifying propylene glycol alginate (PGA) with a microbial-derived coumarin compound (Compound 1) and a fluorinated small molecule (Compound 2), followed by assembly with the silane-based crosslinker ATPMS. The system was subsequently loaded with Dendrobium extract to produce the final nanocomposite material, 2-PGA-1-ATPMS@Dendrobium. This platform exhibited excellent biocompatibility, enhanced cellular uptake, and significant anti-proliferative effects against NSCLC cells. Mechanistic investigations revealed that the nanomaterial induced tumor cell pyroptosis by upregulating the expression of Caspase-1 and GSDMD and promoting the transcription of pro-inflammatory cytokines. Moreover, the nanocomposite demonstrated ultra-sensitive ratiometric fluorescence detection of Cu²⁺ ions, with a detection limit as low as 0.068 nM. Given the critical role of copper ions in inducing cuproptosis and their involvement in tumor progression, this dual-functional nanoplatform presents promising potential for both early diagnosis and targeted treatment of NSCLC.</p> Graphical Abstract <p>Schematic illustration of the dual-functional nanoplatform construction. Compounds 1 and 2 were grafted onto PGA and assembled with ATPMS to form 2-PGA-1-ATPMS, which was then loaded with Dendrobium extract. The final nanocomposite enables ultra-sensitive Cu²⁺ detection and targeted NSCLC therapy via pyroptosis induction.</p> <p></p>

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Polysaccharide-Based Fluorescent Cu²⁺-Responsive Nanocarrier for Dendrobium-Induced Pyroptosis and Inhibition of Non-Small Cell Lung Cancer

  • 期刊论文

  • 发表日期：

    2025年9月3日

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  • Chunmin Dong,
  • Yue Wang

摘要

Non-small cell lung cancer (NSCLC) remains one of the most lethal malignancies worldwide, highlighting the urgent need for the development of novel multifunctional therapeutic strategies. In this study, a bioinspired nanocomposite drug delivery system was designed and constructed by covalently modifying propylene glycol alginate (PGA) with a microbial-derived coumarin compound (Compound 1) and a fluorinated small molecule (Compound 2), followed by assembly with the silane-based crosslinker ATPMS. The system was subsequently loaded with Dendrobium extract to produce the final nanocomposite material, 2-PGA-1-ATPMS@Dendrobium. This platform exhibited excellent biocompatibility, enhanced cellular uptake, and significant anti-proliferative effects against NSCLC cells. Mechanistic investigations revealed that the nanomaterial induced tumor cell pyroptosis by upregulating the expression of Caspase-1 and GSDMD and promoting the transcription of pro-inflammatory cytokines. Moreover, the nanocomposite demonstrated ultra-sensitive ratiometric fluorescence detection of Cu²⁺ ions, with a detection limit as low as 0.068 nM. Given the critical role of copper ions in inducing cuproptosis and their involvement in tumor progression, this dual-functional nanoplatform presents promising potential for both early diagnosis and targeted treatment of NSCLC.

Graphical Abstract

Schematic illustration of the dual-functional nanoplatform construction. Compounds 1 and 2 were grafted onto PGA and assembled with ATPMS to form 2-PGA-1-ATPMS, which was then loaded with Dendrobium extract. The final nanocomposite enables ultra-sensitive Cu²⁺ detection and targeted NSCLC therapy via pyroptosis induction.