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

The in vivo fate of chemotherapeutic drugs plays a vital role in helping the understanding of the therapeutic outcome, side effects, and the mechanism of action. However, the lack of imaging abilities of most drugs, tedious labelling processes, and premature leakage of imaging agents currently result in loss of fidelity between the drugs and any imaging signals. Herein, an unique amphiphilic polymer was created by copolymerization of a NIR-II fluorophore drug 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 was 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 fluorescence imaging both in vitro and in vivo. Polyplatin DT could self-assemble into nanoparticles, referred to as Nanoplatin DT . Furthermore, a caspase-3 cleavable peptide with quenched FRET pairs that serves as an apoptosis protein reporter was attached to Nanoplatin DT , resulting in Nanoplatin DTR that were capable of simultaneously tracking platinum drugs with NIR-II fluorescence and evaluating the therapeutic efficacy with the apoptosis reporters. The strong correlations between the fluorescence intensity of the NIR-II fluorophores and 5'-FAM, and the Pt levels were investigated both in vitro and in vivo with Nanoplatin DTR , enabling a quantitative readout of the platinum levels and feasible evaluation of treatment efficacy. Overall, we reported here the design of the first theranostic polymer with anticancer drugs, drug tracers, and drug efficacy reporters that could work in concert to provide possible insight into the drug fate and mechanism of action in vitro and in vivo. This article is protected by copyright. All rights reserved.