Engineering molecular self-assembly of theranostic nanoprobes for dual-modal imaging-guided precise chemotherapy

Uniting dual-modality of fluorescence and photoacoustic (PA) imaging into theranostic nanoprobes is imperative for spatio-temporally tracking of drug delivery, distribution, and release. Herein, we present a rational design strategy of molecularly precise amphiphilic prodrugs BP n -Cy-S-CPT ( n =0, 5, and 20, refers to the degree of polyethylene glycol (PEG) polymerization; CPT=camptothecin) to tune their self-assembly behaviour, innovatively integrating dual-modal PA and near-infrared (NIR) fluorescence imaging in a single-molecular framework. Among these elaborately designed prodrugs, it is found that only BP 20 -Cy-S-CPT could form uniform and highly stable self-assemblies, especially in showing synergistically enhanced PA and dual-channel NIR signals. In detail, PA signal is employed to trace the in vivo delivery with high spatial resolution, meanwhile the glutathione (GSH)-triggered dual-channel fluorescence response could real-timely monitor drug distribution and release without “blind spot”. The results of in vivo dual-modal PA/NIR imaging have verified that BP 20 -Cy-S-CPT displayed synergistic targeting (including passive, active, and activatable targeting) for tumor-specific delivery, and thereby executed CPT release in the tumor site. Consequently, our molecularly precise BP 20 -Cy-S-CPT self-assemblies could make a breakthrough to spatio-temporally track the in vivo drug release profile, expanding the intelligent theranostic toolbox for precise cancer treatment.