Tumor-targeted nanoplatform for in situ oxygenation-boosted immunogenic phototherapy of colorectal cancer.

Advanced colorectal cancer has a high mortality rate since conventional treatments have limited therapeutic effects and poor prognosis with high risks of metastasis and recurrence. Photodynamic therapy (PDT) is a promising treatment modality for the eradication of colorectal cancer, but its curative efficacy is severely affected by tumor hypoxia. Herein, we developed a core-shell gold nanocage coated with manganese dioxide and hyaluronic acid (AMH) for targeted delivery to colorectal tumors and oxygenation-boosted immunogenic phototherapy in situ. The AMH nanoparticles can generate abundant oxygen from mild acidic/H2O2 medium, which can further enhance the PDT efficacy of AMH itself under near infrared (NIR) irradiation. Meanwhile, AMH-based PDT induced immunogenic cell death (ICD) of tumor cells with damage-associated molecular patterns (DAMPs) release and facilitated the dendritic cells (DCs) maturation to further potentiate the systematic antitumor immunity against advanced tumors. In vivo experiment results exhibited that AMH nanoparticles not only had the ability of targeting tumor but also in situ produced sufficient oxygen to relieve the tumor hypoxia. Furthermore, AMH-mediated oxygen-boosted immunogenic PDT effectively inhibited the tumor growth and recurrence. Thus, this work provides a potent targeted delivery nanoplatform for enhanced immunogenic PDT against advanced cancers. STATEMENT OF SIGNIFICANCE: Local hypoxic tumor microenvironment not only greatly limits the photodynamic therapy (PDT) efficacy, but also has an association with tumor invasiveness and metastasis. This study provides an AMH nanoparticle for targeted delivery to colorectal tumors and oxygenation-boosted immunogenic PDT in situ. AMH nanoparticle exhibits a good tumor-targeted ability to in situ produce abundant oxygen to relieve the tumor hypoxia, and initiates the potent oxygen-boosted immunogenic PDT effect under NIR irradiation to effectively inhibit the growth and recurrence of colorectal tumor. This oxygen-boosted immunogenic PDT nanosystem can be a promising candidate for advanced tumor treatment.