Figure 7. Schematic illustration of the mechanisms by which sorafenib and AZD6244-loaded CTCE-NPs overcome sorafenib treatment escape in HCC.

Sorafenib transactivates RAF dimers and ERK signalling and results in BIM downregulation and PD-L1 upregulation, leading to resistance to sorafenib treatment in HCC. NPs modified with CTCE-9908 co-deliver sorafenib with the MEK inhibitor AZD6244 in HCC, downregulate RAF/ERK and PD-L1 expression, and facilitate intra-tumoral infiltration of cytotoxic CD8+ T cells, resulting in a profound delay in tumor growth.