A relay-type innate immunity activation strategy involving water-soluble NIR-II AIEgen for boosted tumor photo-immunotherapy

<b>Background:</b> Effective innate immunity activation could dramatically improve the anti-tumor efficacy and increase the beneficiary population of immunotherapy. However, the anti-tumor effect of unimodal immunotherapy is still not satisfactory. <b>Methods:</b> Herein, a novel relay-type innate immunity activation strategy based on photo-immunotherapy mediated by a water-soluble aggregation-induced emission luminogen, PEG₄₂₀-TQ, with the assistant of toll-like receptor 7 (TLR-7) agonist, imiquimod (R837), was developed and constructed. <b>Results:</b> The strategy could promote tumor cells to undergo immunogenic cell death (ICD) induced by the well-designed PEG₄₂₀-TQ@R837 (PTQ@R) nanoplatform under light irradiation, which in turn enhanced the infiltration of immune cells and the activation of innate immune cells to achieve the first innate immunity activation. The second innate immunity activation was subsequently achieved by drug delivery of R837 <i>via</i> apoptotic bodies (ApoBDs), further enhancing the anti-tumor activity of infiltrated immune cells. <b>Conclusion:</b> The strategy ultimately demonstrated robust innate immunity activation and achieved excellent performance against tumor growth and metastasis. The construction of the relay-type innate immunity activation strategy could provide a new idea for the application of immunotherapy in clinical trials.