Reactive oxygen species (ROS)‐related therapeutic approaches are developed as a promising modality for cancer treatment because the aberrant increase of intracellular ROS level can cause cell death due to nonspecific oxidation damage to key cellular biomolecules. However, the most widely considered strategy, photodynamic therapy (PDT), suffers from critical limitations such as limited tissue‐penetration depth, high oxygen dependence, and phototoxicity. Non‐photo‐induced ROS generation strategies, which are defined as Xdynamic therapies (X = sono, radio, microwave, chemo, thermo, and electro), show good potential to overcome the drawbacks of PDT. Herein, recent advances in the development of Xdynamic therapies, including the design of systems, the working mechanisms, and examples of cancer therapy application, are introduced. Furthermore, the approaches to enhance treatment efficiency of Xdynamic therapy are highlighted. Finally, the perspectives and challenges of these strategies are also discussed.

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An ideal nanotheranostic agent should be able to achieve efficient tumor accumulation, retention, and fast elimination after its theranostic functions exhausts. However, there is an irreconcilable contradiction on optimum sizes for effective tumor retention and fast elimination. Herein, a programmed size‐changeable nanotheranostic agent based on polyprodrug‐modified iron oxide nanoparticles (IONPs) and aggregation‐induced emission photosensitizer is developed for enhanced magnetic resonance imaging (MRI)‐guided chemo/photodynamic combination therapy. The nano‐sized theranostic agents with an initial diameter of about 90 nm can accumulate in tumor tissue through passive targeting. In the acidic tumor microenvironment, large aggregates of IONPs are formed, realizing enhanced tumor retention and MR signal enhancement. Under the guidance of MRI, light irradiation is applied to the tumor site for triggering the generation of reactive oxygen species and drug release. Moreover, after chemo/photodynamic combination therapy, the large‐sized aggregates are re‐dispersed into small‐sized IONPs for fast elimination, reducing the risk of toxicity caused by long‐term retention. Therefore, this study provides a promising size‐changeable strategy for the development of nanotheranostic agents.

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