Theranostic imaging and multimodal photodynamic therapy and immunotherapy using the mTOR signaling pathway

Tumor metastases are considered the leading cause of cancer-associated deaths. While clinically applied drugs have demonstrated to efficiently remove the primary tumor, metastases remain poorly accessible. To overcome this limitation, herein, the development of a theranostic nanomaterial by incorporating a chromophore for imaging and a photosensitizer for treatment of metastatic tumor sites is presented. The mechanism of action reveals that the nanoparticles are able to intervene by local generation of cellular damage through photodynamic therapy as well as by systemic induction of an immune response by immunotherapy upon inhibition of the mTOR signaling pathway which is of crucial importance for tumor onset, progression and metastatic spreading. The nanomaterial is able to strongly reduce the volume of the primary tumor as well as eradicates tumor metastases in a metastatic breast cancer and a multi-drug resistant patient-derived hepatocellular carcinoma models in female mice. Approaches to combine photodynamic therapy (PDT) with immunotherapy are emerging, allowing the treatment of primary and metastatic tumors. Here the authors report the design and characterization of a nanomaterial for theranostic imaging and photodynamic therapy eliciting anti-tumor immune response in preclinical cancer models.