Development strategies for sorafenib-based targeted radiotheranostic biomaterials: From targeted delivery to multimodal monitoring

Hepatocellular carcinoma (HCC) is one of the significant threats to human health worldwide, and its conventional treatments have obvious limitations. With the development of nanomedicine, the strategy of integrating multiple therapeutic approaches into a single nanoplatform is expected to lead to more efficient treatment of tumors. This study utilizes the nanomaterial PCN-224 as a carrier, labels it with 177 Lu, and modifies its surface with sorafenib (SOR) to construct an integrated diagnostic and therapeutic nanoplatform. The surface modification of SOR not only functions as targeted therapy (TT), but also enhances the active targeting of the nanoparticles and their accumulation at the tumor site. This in vivo distribution could be monitored by dual-modality imaging using fluorescence imaging and SPECT/CT imaging. The long retention allows 177 Lu-mediated radioisotope therapy (RIT) to continue working inside the tumor, thereby improving the limitations of photodynamic therapy (PDT), where the depth of light penetration is limited. Additionally, all three therapeutic modalities can act as inducers of immunogenic cell death (ICD), thereby further enhancing the therapeutic effects by activating the immune response. In conclusion, this work designs a combined triple therapy of PDT-RIT-TT to treat HCC through the direct killing effect and the indirect effect of ICD, utilizing multiple synergistic effects to improve the shortcomings of single therapy, and shows promising prospects for clinical application.