Microenvironment-responsive EGCG-functionalized nanoplatform for synergistic photothermal-chemotherapy against triple-negative breast cancer

Triple-negative breast cancer (TNBC) presents significant therapeutic challenges due to its aggressive nature and lack of molecular targets. To address this challenge, we developed a pH/thermo-responsive nanoplatform based on epigallocatechin-3-gallate (EGCG) modified lipid-coated polydopamine (TEDP), capable of loading doxorubicin (DOX). EGCG, a bioactive polyphenol with high affinity for laminin receptors overexpressed in cancer cells, served both as a targeting ligand and immune microenvironment remodeling regent, enabling selective uptake and remodeling immunosuppression cells. Thermosensitive EGCG modified DOX loaded PDA (TEDP) nanoparticles exhibited spherical morphology (∼140 nm), good colloidal stability, and efficient photothermal conversion under near-infrared irradiation. Under a trigger temperature and pH 6.0, TEDP exhibited pH/temperature-triggered drug release, achieving 70% precise drug release within 4 h, thereby enabling spatiotemporally controlled drug release. Both<i>in vitro</i>and<i>in vivo</i>experiments demonstrated that TEDP nanoparticles could significantly enhance targeting, ensuring precise drug release at the tumor site while minimizing off-target toxicity of DOX. In a TNBC tumor model, the tumor suppression efficacy of TEDP treatment exceeded that of chemotherapy or photothermal therapy (PTT) monotherapy by 3.2-fold and 1.7-fold, respectively. The findings highlighted that TEDP nanoparticles generated synergistic enhancement effects through chemotherapy, PTT and anti-tumor immune responses activating. The multimodal nanoplatform would hold great promise in TNBC therapy, offering a strategy to overcome the limitations of conventional monotherapies.