Transition Metal Complex-Loaded Nanosystems: Advances in Stimuli-Responsive Cancer Therapies

Transition metal complex-loaded nanosystems (TMCNs) represent a cutting-edge platform for stimuli (light, ultrasound)-responsive cancer therapies. These nanosystems, incorporating metals such as manganese(II), zinc(II), ruthenium(II), rhenium(I), iridium(III), and platinum(IV), significantly enhance the efficacy of light-activated therapies, including photodynamic therapy (PDT) and photothermal therapy (PTT), as well as ultrasound-activated treatments like sonodynamic therapy (SDT). TMCNs based on ruthenium(II), rhenium(I), and iridium(III) improve PDT, while manganese(II) and iridium(III) demonstrate exceptional sonosensitizing properties. In PTT, ruthenium(II) and iridium(III)-based TMCNs efficiently absorb light and generate heat. Emerging synergistic approaches that combine SDT, PTT, PDT, chemotherapy, and immunotherapy are demonstrated to be powerful strategies for precision cancer treatment. Zinc(II), ruthenium(II), iridium(III), and platinum(IV)-based TMCNs play a critical role in optimizing these therapies, enhancing tumor targeting, and reducing side effects. Furthermore, TMCNs can amplify immunotherapy by inducing immunogenic cell death, thus strengthening the immune response. These advances address key challenges such as tumor hypoxia and therapeutic resistance, opening new possibilities for innovative photosensitizer-based cancer treatments. This review highlights the latest progress in TMCNs design and applications, demonstrating their potential to revolutionize stimuli-responsive cancer therapies.