Cu 2 ⁺-responsive hyaluronic acid nanoplatform for targeted curcumin delivery and suppression of osteolysis- and metastasis-related phenotypes in lung adenocarcinoma

Bone metastasis is a major cause of morbidity and mortality in lung adenocarcinoma and is closely associated with epithelial–mesenchymal transition (EMT) and tumor-derived osteolytic factors. Although curcumin exhibits promising anti-tumor and anti-metastatic activities, its poor solubility and low bioavailability limit its therapeutic application. In this study, a Cu 2 ⁺-responsive hyaluronic acid nanoplatform modified with compound 1 (1-HA) was developed for targeted curcumin delivery (1-HA@Cur) and Cu 2 ⁺-responsive fluorescence sensing. The physicochemical properties, Cu 2 ⁺ sensing performance, and biological effects of 1-HA@Cur were systematically evaluated under in vitro conditions using A549 lung adenocarcinoma cells. Compared with free curcumin, 1-HA@Cur exhibited enhanced antiproliferative activity and induced a significant dose-dependent reduction in cell viability. Enzyme-Linked Immunosorbent Assay (ELISA) analysis demonstrated that nanoparticle treatment significantly decreased the secretion of parathyroid hormone-related protein (PTHrP), a key mediator involved in osteolytic signaling. Furthermore, qRT-PCR analysis revealed that 1-HA@Cur modulated EMT-associated molecular changes, characterized by reduced Vimentin expression and increased E-cadherin expression. Collectively, these findings demonstrate that 1-HA@Cur effectively suppresses lung adenocarcinoma cell growth and attenuates osteolytic- and metastasis-related phenotypes in vitro . This multifunctional nanoplatform integrates targeted curcumin delivery with Cu 2 ⁺-responsive fluorescence sensing, providing a potential strategy for lung adenocarcinoma therapy and copper-ion-associated microenvironment analysis, while further validation in more complex biological models is required.