Overcoming multiple barriers to deliver photo-gene system for glioma-targeted combined therapy.

Overcoming multiple barriers to deliver macromolecular drugs is an urgent challenge for glioma treatment. Herein, a strategy of protein corona-regulation synergizing with photoactivation based on T10 peptide-modified and indocyanine green (ICG)-loaded dendrigraft poly-L-lysines was proposed to augment prime editing therapy of glioma. First, the modified T10 peptide could escape the interference barrier of protein crown in blood via its specific binding with endogenous transferrin, thus crossing the blood-brain barrier (BBB) and achieving the targeting recognition of glioma cells. Next, the loaded ICG could weaken the tumor stromal barrier, decrease the cell membrane barrier and escape the lysosomal degradation/autophagy barrier via its photothermal and photodynamic effects. Subsequently, a therapeutic gene that could downregulate p-ERK1/2 for tumor growth inhibition and immunoregulation could be effectively delivered into the glioma cells. The glioma-targeted photo-gene combined immunotherapy effectively inhibit the glioma growth, especially co-dosing with the PD-1 antibody.