A Dragon‐Fruit‐Like Nanoplatform Containing Polydopamine‐Wrapped Selenium Quantum Dots Boosts Synergistic Chemo‐Photothermal Therapy for Triple‐Negative Breast Cancer

ABSTRACT

Triple‐negative breast cancer (TNBC) remains a significant clinical challenge due to lack of targetable biomarkers and systemic toxicity of conventional chemotherapy. To address these hurdles, we engineered a bioinspired “dragon‐fruit‐mimetic” nanoplatform (GemSe@PDA), with selenium quantum dots (SeQDs) and gemcitabine (Gem) uniformly dispersed in polydopamine (PDA) matrix that acts as a functional photothermal carrier. This distinctive structural endows high drug loading capacity, and the PDA matrix degrades under lysosomal acidic conditions (pH ∼5.0), enabling stimuli‐responsive release of SeQDs and Gem. GemSe@PDA shows uniform morphology (174.8 nm in diameter) and excellent photothermal capability of raising local temperature to 48.3°C within 10 min. Functionally, the GemSe@PDA nanoplatform integrates three modalities of SeQD‐driven apoptosis, PDA‐mediated photothermal ablation under 808 nm NIR irradiation, and Gem‐induced chemotherapy. Mechanistically, RNA‐seq analysis revealed that SeQDs provoke apoptosis by regulating the Akt/caspase‐3 signaling pathway, while Gem triggers cell cycle arrest. In vivo studies demonstrated that GemSe@PDA markedly boosts tumor‐targeted accumulation and effectively suppresses tumor growth, lowering the tumor weight to merely 15.9% of the control group without systemic toxicity. By combining the structural advantages of a dragon fruit‐like design with bioactive SeQDs, this nanoplatform provides a versatile, biocompatible strategy for overcoming the therapeutic problems of TNBC.