Tumor microenvironment-responsive nanoparticles composed of hyaluronic acid and stearic acid for the treatment of lung metastasis in triple-negative breast cancer.

Triple-negative breast cancer lung metastasis is a key challenge in its treatment. We herein present an intelligent nanoparticle delivery platform, HCS, which was fabricated by synthesizing a polymer long-chain SA-CY-HA (HCS) through a two-step amidation reaction utilizing stearic acid (SA), cystamine dihydrochloride (CY), and hyaluronic acid (HA). This platform facilitates the co-delivery of paclitaxel (PTX) and honokiol (Hol), thereby concurrently suppressing tumor growth and lung metastasis. HCS can encapsulate the hydrophobic soluble drugs PTX and Hol internally, enhancing their solubility and enabling a specific response to the tumor microenvironment. In vitro experiments demonstrated that HCS@PTX + Hol effectively suppressed the proliferation, migration, and invasion of tumor cells. Furthermore, we observed that HCS@PTX + Hol downregulated the expression of MMP2 and MMP9. In vivo experiments indicated that HCS@PTX + Hol significantly inhibited tumor growth and limited lung metastasis. Overall, our designed intelligent nanoparticle delivery platform HCS@PTX + Hol exhibits potent anti-tumor effects, warranting further development and application.