A visible light-promoted difluoroalkylation reaction of arenes or heterocycles, using triaryl phosphine as the catalyst and difluoroalkyl iodide as the alkylating agent, is presented. The strategy is highlighted by photocatalyst-free, mild reaction conditions and a broad substrate scope. Mechanistic experiments indicate that this reaction involves a radical-chain process that is initiated by an electron donor−acceptor complex formed from difluoroalkyl iodide and phosphine.

The limited lymphocyte infiltration and exhaustion of tumoricidal functions in solid tumors remain a formidable obstacle to cancer immunotherapy. Herein, we designed a macrophage membrane-coated nano-gemcitabine system (MNGs) to promote lymphocyte infiltration and then synergized anti-programmed death ligand 1 (antiPD-L1) to reinvigorate the exhausted lymphocytes. MNGs exhibited effective intratumor-permeating and responsive drug-releasing capacity, produced notable elimination of versatile immunosuppressive cells, and promoted lymphocyte infiltration into cancer cell regions in tumors, but over 50% of these infiltrated lymphocytes were in the exhausted state. Compared with MNG monotherapy, the MNGs+antiPD-L1 combination produced 31.77% and 30.63% reduction of exhausted CD3 + CD8 + T cells and natural killer (NK) cells and 2.83-and 3.17-fold increases of interferon-γ (IFN-γ)-positive subtypes, respectively, thereby resulting in considerable therapeutic benefits in several tumor models. Thus, MNGs provide an encouraging strategy to promote lymphocyte infiltration and synergize antiPD-L1 to restore their tumoricidal function for cancer immunotherapy.