Singlet oxygen-responsive nanoplatform for synergetic photodynamic-immunotherapy guided by NIR-II imaging
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PUBLIC SUMMARY
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This study develops a light-activated system to improve therapy for triple-negative breast cancer.
The nanoparticle uses CRISPR/Cas9 to edit the PD-L1 gene and a light-triggered therapy to kill tumor cells.
The two methods work together to reshape the tumor's immune environment and enhance anti-tumor immunity.
The system is monitored using advanced near-infrared imaging.
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ABSTRACT
Triple-negative breast cancer (TNBC) presents significant treatment challenges due to its lack of clear molecular targets and immunosuppressive tumor microenvironment (TME). This study reports the development of a light-triggered biomimetic nanodelivery system (OPTC-RNP@CM) to overcome these hurdles. The system integrates a semiconducting polymer for second near-infrared (NIR-II) imaging, a photosensitizer (Ce6), and CRISPR/Cas9 ribonucleoprotein targeting PD-L1 via a singlet oxygen-cleavable linker. Coated with homologous tumor cell membranes for enhanced targeting, the nanoparticles accumulate at the tumor site. Upon NIR irradiation, generated singlet oxygen simultaneously triggers the release of Cas9 RNP for PD-L1 gene editing and induces photodynamic therapy (PDT). This dual action promotes immunogenic cell death (ICD) and, synergistically with PD-1/PD-L1 pathway blockade, effectively remodels the immunosuppressive TME, amplifying the antitumor immune response. This versatile platform offers a promising strategy for precise and enhanced immunotherapy against TNBC. -
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REFERENCES
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Ji Y., Qian J., Fan L., et al. (2026). Singlet oxygen-responsive nanoplatform for synergetic photodynamic-immunotherapy guided by NIR-II imaging. The Innovation Materials 4:100190. https://doi.org/10.59717/j.xinn-mater.2026.100190
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Ji Y., Qian J., Fan L., et al. (2026). Singlet oxygen-responsive nanoplatform for synergetic photodynamic-immunotherapy guided by NIR-II imaging. The Innovation Materials 4:100190. https://doi.org/10.59717/j.xinn-mater.2026.100190
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Figure 1.
Basic characterization of the OPTC-RNP@CM synthesis pro-cess and in vitro protein release experiments
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Figure 2.
In vitro cell-based validation experiments
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Figure 3.
The distribution of OPTC-RNP@CM in vivo after intravenous injection in breast cancer-bearing mice
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Figure 4.
Synergistic triple-negative breast cancer immunotherapy via gene editing and photodynamic therapy utilizing OPTC-RNP@CM in vivo
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Figure 5.
Synergistic activating T cell-mediated anti-tumor immunity by targeting PD-L1 and PDT
