Mn(II)-directed dual-photosensitizers co-assemblies for multimodal imaging-guided self-enhanced phototherapy

Phototherapy has attracted increasing attention in cancer therapy owing to its non-invasive nature, high spatiotemporal selectivity, and negligible side effects. However, a single photosensitizer often exhibits poor photothermal conversion efficiency or insufficient reactive oxygen species (ROS) productivity. Even worse, the ROS can be consumed by tumor overexpressed reductive glutathione, resulting in severely compromised phototherapy. In this paper, we prepared a Mn^II-coordination driven dual-photosensitizers co-assemblies (IMCP) for imaging-guided self-enhanced PDT/PTT. Specifically, a photothermal agent indocyanine green (ICG), a photodynamic agent chlorin e6 (Ce6), and a transition metal ion (Mn^II/III) were chosen to synthesize the nanodrug via coordination-driven co-assembly. The as-prepared IMCP exhibited extremely high photosensitizer payload (96 wt%), excellent physiological stability, and outstanding tumor accumulation. Moreover, the existence of Mn^II not only assists the nanostructure formation but also could competitively coordinate with GSH to minimize the unnecessary ROS consumption, thus improving PDT efficiency. Meanwhile, benefiting from the intrinsic fluorescence, photoacoustic imaging ability of photosensitizers, and the MRI contrast potential of Mn^II/III, IMCP exhibited superior imaging potential for guiding tumor phototherapy. By changing the excitation wavelength suitably, IMCP could realize the switch between PTT and PDT. In short, the dual-PSs co-assembled nanotheranostic has great potential for multi-modal imaging guided phototherapy.