Transformable Nanotheranostics Capable of Sensoring Nucleic Acid Drugs’ Spatiotemporal Behaviors

Nanotheranostics facilitates personalized treatment by providing imaging capabilities for nucleic acid drug vectors. However, available nanotheranostics are not yet capable of indicating the release behavior of nucleic acid drugs. Herein, four guidelines for the design of nanotheranostics are proposed. Under the guidance, transformable nanotheranostics are prepared that can sense the spatiotemporal behaviors of siRNA accumulation and release to facilitate personalized oncology treatment. The nanotheranostics sense the spatiotemporal accumulation behavior of siRNA in tumors through computerized tomography. Besides, the tumor cytoplasmic microenvironment mediates both siRNA release and nanotherapeutic agent transformation simultaneously. The transformation‐activated magnetic resonance imaging (MRI) signals sense the spatiotemporal release behavior of siRNA. Moreover, the therapeutic effect of survivin‐targeted siRNA can be diagnosed and confirmed by contrast‐enhanced CT/MRI multi‐modal imaging in real‐time. The transformable nanotheranostics further promote personalized oncotherapy by nucleic acid drugs. These four guidelines are expected to direct the research and development of nucleic acid drug‐based nanotheranostics. This study also provides a new perspective on real‐time sensoring the spatiotemporal behaviors of nucleic acid drugs in vivo. AuSGTPsS are designed to sense the spatiotemporal behaviors of nucleic acid drugs. Since, siRNA, vectors, and contrast agents are bound by covalent interaction, the accumulation behavior of siRNA is sensed by computerized tomography. After entering the lesion, the release of siRNA is accompanied by the aggregation of magnetic resonance imaging contrast agents, so the release behavior of nucleic acid drugs is precisely sensed.