Breast cancer remains the most prevalent malignancy among women and the second leading cause of cancer-related mortality worldwide, primarily attributable to delayed diagnosis and limited therapeutic efficacy. Recent nanotechnology advances exhibit transformative potential in breast cancer management. Metal-organic frameworks (MOFs) have emerged as promising nanoplatforms for biomedical applications due to their exceptional adsorption capacity, high surface area, tunable porosity, structural stability, and facile surface functionalization-properties enabling advanced drug delivery systems (DDSs). This review systematically summarizes MOFs for DDSs and their applications in breast cancer. Classification by metal-ligand composition precedes critical analysis of synthesis methodologies, including comparative advantages and limitations alongside key factors influencing biomedical performance. A dedicated sections highlights normal and stimuli-responsive MOFs activated by endogenous or exogenous triggers. Furthermore, the application of multifunctional MOFs has been comprehensively explored, including chemotherapy, photothermal therapy, photodynamic therapy, immunotherapy, and diagnostic-therapeutic integration in breast cancer. Finally, challenges and possible solutions for MOFs in drug delivery are discussed.
Potassium-based MOFs (K-MOFs) demonstrate dual-functionality: their porous architectures facilitate energy-relevant processes (eg, selective ion transport, catalytic reactions, and gas adsorption), while exhibiting minimal cytotoxicity and environmental compatibility advantageous for drug delivery. The preferred organic ligand is cyclodextrin. An example: He et al pioneered nanoscale cyclodextrin metal-organic frameworks (CD-MOFs) for azilsartan (AZL) encapsulation, employing a methanol-mediated crystallization protocol with PEG20000 as a crystallizing agent. This methodology yielded high-purity CD-MOFs enabling efficient AZL loading (17.2 ± 0.8 wt%), synergistically enhancing aqueous solubility by 340-fold and oral bioavailability by 9.7-fold versus free AZL [2].
[1] Jiang XR, Mi J, Wang Y, Yin M, Tong Y, Zhu Y. Application of Metal-Organic Frameworks Nanoparticles in the Diagnosis and Treatment of Breast Cancer. Int J Nanomedicine. 2025;20:10127-10149
https://doi.org/10.2147/IJN.S534422
[2] He Y, Zhang W, Guo T, et al. Drug nanoclusters formed in confined nano-cages of CD-MOF: dramatic enhancement of solubility and bioavailability of Azilsartan. Acta Pharmaceutica Sinica B. 2019;9(1):97–106. https://doi.org/10.1016/j.apsb.2018.09.003