Breast cancer has a high mortality rate and is one of the most common malignancies among women. Conventional therapies such as radiotherapy, chemotherapy, and surgery are not sufficiently effective and have notable drawbacks, including toxicity and damage to healthy cells, resulting in an unsatisfactory prognosis. Photothermal therapy (PTT) and combinatory therapies have emerged as a promising therapeutic paradigm for breast cancer treatment to achieve precise, minimally invasive tumor ablation with real-time imaging guidance, synergistic therapeutic effects, reduced systemic toxicity, enhanced immune activation, and improved outcomes against recurrence, metastasis, and drug resistance. These approaches utilize near-infrared light to visualize tumor margins and locally generate hyperthermia to destroy cancerous tissue. The development of novel nanomaterials has significantly enhanced the efficacy of breast cancer treatments. This review explores the mechanisms, current advancements, and clinical potential of PTT and combinatory therapy in breast cancer treatment, with an emphasis on developments to a three-level progression: material innovation, targeted delivery, and multimodal synergy. Special focus is given to the rapidly advancing image-guided PTT in combination with other treatment modalities for precise and effective treatment of breast cancer. Furthermore, the review addresses the challenges and future directions in translating these technologies from preclinical models to clinical settings, including the optimization of imaging resolution and thermal efficiency, while minimizing potential side effects. We hope this perspective offers valuable insights into PTT and combinatory therapies for breast cancer and contributes to advancing their clinical translation, ultimately enhancing women’s health.

Metastatic breast cancer (MBC) remains one of the most aggressive and fatal malignancies in women, primarily due to tumor heterogeneity, multidrug resistance, and the limitations of conventional therapeutic approaches. Aim: This review aims to evaluate recent advances in nanomaterial-based photothermal therapy (PTT) platforms and their potential in the treatment of metastatic breast cancer. Method: A comprehensive analysis of current literature was conducted to examine how various nanomaterials are engineered for targeted PTT, with particular emphasis on their mechanisms of action, synergistic applications with chemotherapy, immunotherapy, and photodynamic therapy, as well as their capacity to overcome challenges associated with targeting metastatic niches. Results: The findings indicate that nanotechnology-enabled PTT provides spatiotemporal precision, efficient tumor ablation, and reduced systemic toxicity, while significantly enhancing therapeutic outcomes when integrated into multimodal treatment strategies. Recent preclinical studies and early clinical trials further underscore advancements in imaging guidance, thermal efficiency, and site-specific drug delivery; however, issues related to biocompatibility, safety, and large-scale clinical translation remain unresolved. Conclusions: Nanomaterial-assisted PTT holds substantial promise for improving therapeutic efficacy against metastatic breast cancer. Future research should prioritize optimizing imaging resolution, minimizing adverse effects, and addressing translational challenges to accelerate clinical integration and ultimately enhance health outcomes for women.

As surgery is the first-line paradigm for many solid tumors, precision in preoperative diagnosis and intraoperative imaging is of significant importance. Dual MRI and NIR-II fluorescence imaging could fulfill precision imaging requirements in treating cancers, because of its deep penetration and real-time high spatiotemporal resolution. Thus, the design of dual MRI/NIR-II fluorescence contrast agents is crucial for the diagnosis and surgery of cancers. Herein, we developed optically transparent NaGdF4 matrix-based downshifting nanoparticles (DSNPs) co-doped with Nd³⁺, Yb³⁺, and Er³⁺ as a single nanoplatform for dual NIR-II fluorescence and T1-weighted MRI. Systematic dopant engineering reveals that optimal Nd³⁺ loading enhances cascade Nd → Yb → Er energy transfer and yields intense NIR-II emission at 1334 and 1521 nm upon 808 nm excitation with a relative quantum yield of 1.55, while the presence of Gd³⁺ in the optically transparent matrix imparts strong T1 contrast (4.98 s⁻¹ mM⁻¹). The Pluronic F-127 surface coating confers colloidal stability and biocompatibility. In vitro assays confirm negligible cytotoxicity and efficient cellular uptake. In vivo studies in subcutaneous 4T1 tumor-bearing mice demonstrate robust accumulation, high tumor-to-background contrast in both MRI/NIR-II fluorescence and enable precise NIR-II fluorescence imaging-guided surgery with real-time margin visualization. Therefore, dopant-engineered DSNPs represent a promising dual-modal imaging agent for deep-tissue diagnostic and real-time surgical guidance in precision oncology.