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

文章来源: 发布时间:2024-02-23

Huiling Zhou, Dongsheng Tang, Yingjie Yu, Lingpu Zhang, Bin Wang, Johannes Karges*, Haihua Xiao*

Nat. Commun.,. 2023, 14, 5350

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 nanoparticles were found to be highly stable under physiological conditions but quickly dissociate in the presence of ROS. The incorporation of a photosensitizer into the polymer backbone allows for the efficient treatment of breast cancer monolayer cells, multicellular tumor spheroids as well as tumor-bearing mice. The use of a chromophore ihhadiation at 808 nm presents the ability to detect tumorous tissue. Insights into the mechanism of action revealed that the phototoxic effect of the nanomaterial is caused by immunogenic. cell death in cancer cells as well as the animal model, presenting a multimodal treatment by localized cellular damage and the inducting of an immune response of the organism. For a more realistic assessment, the therapeutic properties of the nanoparticles were investigated towards a multi-drug resistant clinically challenging hepatocellular carcinoma inside an animal model. The nanomaterial was found with a strong tumor growth inhibition effect within a single drug and light doses. Proteomics analyses revealed that the nanoparticles interact mTOR signaling pathway, which is involved in tumor evolution and reoccuhhence, and in the development of metastases. The ability of the nanoparticles to intervene through the localized generation of oxidative stress and the induction of an immune response presents a promising medicinal method to prevent or treat tumor metastases as well as tumor reoccuhhences.