Copper and Iron-Based Metal-Organic Frameworks for Synergistic Cancer Phototherapies: Recent Advances, Challenges, and Future Prospects

Current treatments for cancer such as surgery, chemotherapy, radiotherapy, and chemodynamic therapy often exhibit poor efficacy and severe side effects; this, cancer remains a major global health challenge. In the ongoing exploration of therapeutic strategies with improved outcomes and reduced adverse effects, phototherapies (PTs), including photothermal (PTT) and photodynamic therapy (PDT), are gaining attention due to their non-invasive and targeted nature, resulting in reduced side effects. However, further material optimizations are needed to enhance PT performance. Metal-organic frameworks (MOFs) have emerged as promising PTT/PDT nanoplatforms due to their tunable structures, high surface area, and ability to host photoactive agents. Their porous architecture facilitates efficient photosensitizer encapsulation and promotes light-induced thermal effects, improving therapeutic stability and efficacy. The therapeutic potential of MOFs is further enhanced when combined with multiple treatment modalities. This review focuses on the roles of Fe/Cu-based MOFs in PTs, their synthesis, underlying mechanisms in PTT/PDT, and recent design advancements. It also summarizes the progress in Cu/Fe-MOF nanocomposite development over the past 5 years, from construction to synergistic applications. These insights can inform future efforts in the clinical translation of Cu/Fe-MOFs in cancer theranostics.