Programmed Size‐Changeable Nanotheranostic Agents for Enhanced Imaging‐Guided Chemo/Photodynamic Combination Therapy and Fast Elimination

Abstract 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.