Abstract
Triple-negative breast cancer (TNBC) is the most malignant subtype of breast cancer, characterized by aggressive malignancy and a poor prognosis. Emerging nanomedicine-based combination therapy represents one of the most promising strategies for combating TNBC. Polypyrrole nanoparticles (PPY) are excellent drug delivery vehicles with outstanding photothermal performances. However, the impact of morphology on PPY's drug loading efficiency and photothermal properties remains largely unexplored. In this study, we propose that pluronic P123 can assist in the synthesis of polypyrrole nanoparticles with rough surfaces (rPPY). During the synthesis, P123 formed small micelles around the nanoparticle surface, which were later removed, resulting in small pits and cavities in rPPY. Subsequently, the rPPY was loaded with the chemotherapy drug gemcitabine (Gem@rPPY) for chemo-photothermal therapy against TNBCs. Our results demonstrate that rPPY exhibited superior photothermal performance and significantly enhanced drug loading efficiency by five times compared to smooth PPY nanoparticles. In vitro assessments confirmed Gem@rPPY's robust photothermal properties by efficiently converting light into heat. Cell culture experiments with 4T1 cells and a TNBC mice model revealed significant tumor suppression upon Gem@rPPY administration, emphasizing its efficacy in inducing apoptosis. Toxicity evaluations demonstrated minimal adverse effects both in vitro and in vivo, highlighting the biocompatibility of Gem@rPPY. Overall, this study introduces a promising combination therapy nanoplatform that underscores the importance of surface engineering to enhance therapeutic outcomes and overcome current limitations in TNBC therapy.