Triple-negative breast cancer (TNBC) has been listed as one of the most fatal diseases, and no effective targeting treatment is clinically available. Although CD44-targeting hyaluronic acid (HA) has been utilized as targeting ligands in many studies, no facile ways have been developed through HA self-assembly at the nanoparticle surface. Herein, we reported N-isopropylacrylamide-grafted chitosan-based nanoparticles self-assembling with HA (HA-NPs) through electrostatic forces and loaded with curcumin (CUR). The HA-NPs displayed pH-responsive properties due to the chemical modification of chitosan, and the preparation process was optimized by central composite design–response surface methodology. HA anchorage confers the vehicle with tumor-targeting capability. HA-NPs displayed more robust effects of inhibiting TNBC primary tumor growth than free CUR and a plain counterpart but without increased systemic cytotoxicity. In addition, in vivo pharmacokinetic studies showed that HA-NPs significantly increased the in vivo residence time of free CUR and improved the bioavailability of CUR. These findings suggested that chitosan-based HA-NPs may provide a feasible and unique strategy to achieve CD44 targeting and enhance its efficacy in vivo for the treatment of advanced TNBC.

Natural products, originating from diverse biological sources, serve as a critical reservoir of bioactive compounds for cancer intervention across prevention, treatment, and supportive care. Their mechanisms extend beyond direct cytotoxicity to include modulation of tumor metabolism—such as glucose, lipid, and glutamine pathways—and the tumor microenvironment (TME), highlighting their multifaceted role in oncology. However, a systematic synthesis of how natural products concurrently target metabolic reprogramming and immune–stromal components across different clinical phases remains lacking. This review delineates the therapeutic applications of natural products—such as flavonoids, alkaloids, and terpenoids—across the clinical continuum, including perioperative support, concurrent chemoradiotherapy, maintenance therapy, and metastasis suppression. We detail their actions in disrupting core metabolic pathways and elucidate their influence on TME components like cancer‐associated fibroblasts, extracellular matrix, and immune cells including tumor‐associated macrophages and T lymphocytes. Furthermore, we discuss innovative delivery strategies—including nanocarriers and codelivery systems—that enhance bioavailability and enable synergistic combination with chemotherapy or immunotherapy. By integrating mechanistic insights with clinical translation strategies, this work provides a comprehensive framework for employing natural products in biomarker‐driven, precision oncology regimens, supporting their evolving role in multimodal cancer care.

Breast cancer, the most prevalent malignant tumor among women globally, is significantly influenced by the Wnt/β-catenin signaling pathway, which plays a crucial role in its initiation and progression. While conventional chemotherapy, the standard clinical treatment, suffers from significant drawbacks like severe side effects, high toxicity, and limited prognostic efficacy, Traditional Chinese Medicine (TCM) provides a promising alternative. TCM employs a multi-targeted therapeutic approach, which results in fewer side effects and offers a high potential for effective treatment. This paper presents a detailed analysis of the therapeutic impacts of TCM on various subtypes of breast cancer, focusing on its interaction with the Wnt/β-catenin signaling pathway. Additionally, it explores the effectiveness of both monomeric and compound forms of TCM in the management of breast cancer. We also discuss the potential of establishing biomarkers for breast cancer treatment based on key proteins within the Wnt/β-catenin signaling pathway. Our aim is to offer new insights into the prevention and treatment of breast cancer and to contribute to the standardization of TCM.