Developing effective immunotherapies with low toxicity and high tumor specificity is the ultimate goal in the battle against cancer. Here, we reported a cell-membrane immunotherapy strategy that was able to eliminate primary tumors and inhibited distant tumors by using natural killer (NK) cell membrane cloaked photosensitizer 4,4′,4′′,4′′′-(porphine-5,10,15,20-tetrayl) tetrakis (benzoic acid) (TCPP)-loaded nanoparticles (NK-NPs). The proteomic profiling of NK cell membranes was performed through shotgun proteomics, and we found that NK cell membranes enabled the NK-NPs to target tumors and could induce or enhance pro-inflammatory M1-macrophages polarization to produce antitumor immunity. The TCPP loaded in NK-NPs could induce cancer cell death through photodynamic therapy and consequently enhanced the antitumor immunity efficiency of the NK cell membranes. The results confirmed that NK-NPs selectively accumulated in the tumor and were able to eliminate primary tumor growth and produce an abscopal effect to inhibit distant tumors. This cell-membrane immunotherapeutic approach offers a strategy for tumor immunotherapy.

Nature has always inspired robotic designs and concepts. It is conceivable that biomimic nanorobots will soon play a prominent role in medicine. The "Terminator" in the science fiction film is a cybernetic organism with living tissue over a metal endoskeleton, which inspired us to develop natural-killer-cell-mimic nanorobots with aggregation-induced emission (AIE) characteristics (NK@AIEdots) by coating a natural kill cell membrane on an AIE-active polymeric endoskeleton, PBPTV, a highly bright NIR-II AIE-active conjugated polymer. Owing to the AIE and soft-matter characteristics of PBPTV, as-prepared NK@AIEdots maintained a superior NIR-II brightness (quantum yield ∼7.9% in water) and good biocompatibility. Besides, they can serve as a tight junction (TJ) modulator to trigger an intracellular signaling cascade, causing TJ disruption and actin cytoskeleton reorganization to form an intercellular "green channel" to help them to cross the blood−brain barrier (BBB) silently. Furthermore, they can initiatively accumulate in glioblastoma cells in the complex brain matrix for highcontrast and through-skull tumor imaging. The tumor growth was also greatly inhibited by these NK@AIEdots under the NIR light illumination. As far as we know, the quantum yield of PBPTV is the highest among the existing NIR-II luminescent conjugated polymers. Besides, the NK-cell biomimetic nanorobots showed great potential for BBB-crossing active delivery.

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