A Polyplatin with Hands‐Holding Near‐Infrared‐II Fluorophores and Prodrugs at a Precise Ratio for Tracking Drug Fate with Realtime Readout and Treatment Feedback

Abstract The in vivo fate of chemotherapeutic drugs plays a vital role in understanding the therapeutic outcome, side effects, and the mechanism. However, the lack of imaging abilities of drugs, tedious labeling processes, and premature leakage of imaging agents result in loss of fidelity between the drugs and imaging signals. Herein, an amphiphilic polymer is created by copolymerization of a near‐infrared‐II (NIR‐II) fluorophore tracer (T) and an anticancer Pt(IV) prodrug (D) of cisplatin in a hand‐holding manner into one polymer chain for the first time. The obtained Polyplatin DT is capable of delivering the drugs and the fluorophores concomitantly at a precise D/T ratio, thereby resulting in tracking the platinum drugs and even readout of them in real‐time via NIR‐II imaging. Polyplatin DT can self‐assemble into nanoparticles, referred to as Nanoplatin DT . Furthermore, a caspase‐3 cleavable peptide that serves as an apoptosis reporter is attached to Nanoplatin DT , resulting in Nanoplatin DTR that are capable of simultaneously tracking platinum drugs and evaluating the therapeutic efficacy. Overall, it is reported here the design of the first theranostic polymer with anticancer drugs, drug tracers, and drug efficacy reporters that can work in concert to provide insight into the drug fate and mechanism of action.