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

Background: 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. Methods: 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. Results: 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 via apoptotic bodies (ApoBDs), further enhancing the anti-tumor activity of infiltrated immune cells. Conclusion: 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.

Immunoadjuvant Nanoparticles as Trojan Horses for Enhanced Photo-Immunotherapy in the Treatment of Triple-Negative Breast Cancer.

Treatment of triple-negative breast cancer (TNBC) faces great challenges due to high invasiveness and poor prognosis. Therefore, effective treatment methods are urgently needed to control primary tumors and suppress distant tumors. Herein, we employed glycated chitosan (GC), a polysaccharide macromolecular immunoadjuvant, to construct a self-assembly GC@ICG nanoparticle which is accessible to tumor cells for synergistic cancer treatment based on the combination of phototherapy and immunotherapy. In this strategy, the self-associated synthesis of spherical GC@ICG significantly improved the stability of ICG and endowed GC with Trojan Horses in tumor cells to enhance tumor immunogenicity. A bilateral 4T1 tumor-bearing mouse model was established to evaluate the therapeutic outcomes and specific host antitumor immune response. Finally, GC@ICG-based phototherapy can directly eliminate primary tumors and resist the progression of untreated distant tumors. In addition, compared to the treatment of L + GC + ICG, GC@ICG-based phototherapy was evidenced to suppress lung metastasis and enhance infiltration of CD8+ T cells in untreated distant tumors. Therefore, this design shows promise in addressing the challenges of the treatment of TNBC.