Manganese-Based Natural Photosensitive Protein Nanocomplex for Image-Guided Multimodal Synergistic Cancer Therapy

Photodynamic therapy (PDT) is widely utilized in cancer treatment as a noninvasive strategy. Phycocyanin (PC), a natural water-soluble photosensitizer with nontoxic properties, shows promise as a PDT candidate. However, the limitations of PC when used alone in PDT for cancer treatment, such as inadequate tumor delivery and weak efficacy, must be addressed. Herein, an efficient theranostic manganese (Mn)-based PC nanocomplex (PC@Mn) was synthesized through a straightforward one-pot self-assembly reaction for synergistic antitumor therapy. The PC@Mn nanoparticles were found to have a suitable size (∼129 nm) and demonstrated excellent biocompatibility and biosafety. Importantly, these nanoparticles exhibited enhanced biodistribution with improved tumor targeting and retention properties. When combined with 650 nm laser irradiation, PC@Mn showed a significant enhancement in the PDT effect in vivo. Additionally, PC@Mn displayed promising magnetic resonance (MR) imaging capabilities, with a high relaxation rate (<i>r</i>₁ = 10.14 mM^-1 s^-1) and an extended imaging time window (4 h). This feature enables real-time monitoring of the nanoparticles' distribution within tumors, facilitating precise determination of the optimal PDT treatment time. Overall, the study highlights PC@Mn as a simple, safe, and highly efficient strategy for synergistic antitumor therapy. Its ability to combine PDT with MR imaging for real-time guidance represents an efficient approach to cancer treatment, promising improved therapeutic outcomes and potential clinical applications in the future.