Engineered EGCG-Containing Biomimetic Nanoassemblies as Effective Delivery Platform for Enhanced Cancer Therapy

Nano-based immunotherapy of therapeutic biomolecules is attractive but tremendously hampered by the poor delivery efficiency. This study reports a novel delivery system of fluorinated-coordinative-epigallocatechin gallate (EGCG), referring as FEGCG/Zn, through the integration of fluorination and zinc ions (Zn²⁺ ) into EGCG. The robust therapeutics of FEGCG/Zn are measured in terms of the regulating effect on programmed cell death ligand 1 (PD-L1), the effective delivery of diverse biomolecules, and the hitchhiking ability using living cells. Taking small interfering RNA of PD-L1 (siPD-L1) and erythrocytes as an example, the fabricated biomimetic system achieves excellent siPD-L1 delivery and further improves siPD-L1 accumulation in tumors. Finally, the combination of FEGCG/Zn and siPD-L1 promotes antitumor immunotherapy through alleviation of T cells exhaustion by regulating PD-L1 expression in tumor cells. The results demonstrate that FEGCG/Zn substantially regulates PD-L1 expression and improves immune-biomolecule delivery by forming biomimetic nanoassemblies, offering a versatile platform for cancer immunotherapy.