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

Abstract

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.