Shengchang Tao,Yuchen Song,Shaobo Ding,Ruirong He,Qiankun Shi,Fang Hu
Photodynamic therapy (PDT) eradicates tumors via the generation of toxic reactive oxygen species (ROS) by activation of a photosensitizer (PS) with appropriate light. Local PDT toward tumors can trigger the immune response to inhibit distant tumors, but the immune response is usually insufficient. Herein, we used a biocompatible herb polysaccharide with immunomodulatory activity as the carrier of PS to enhance the immune inhibition of tumors after PDT. The Dendrobium officinale polysaccharide (DOP) is modified with hydrophobic cholesterol to serve as an amphiphilic carrier. The DOP itself can promote dendritic cell (DC) maturation. Meanwhile, TPA-3BCP are designed to be cationic aggregation-induced emission PS. The structure of one electron-donor linking to three electron-acceptors endows TPA-3BCP with high efficiency to produce ROS upon light irradiation . And the nanoparticles are designed with positively charged surfaces to capture antigens released after PDT, which can protect the antigens from degradation and improve the antigen-uptake efficiency by DCs. The combination of DOP-induced DC maturation and antigen capture-increased antigen-uptake efficiency by DCs significantly improves the immune response after DOP-based carrier-mediated PDT. Since DOP is extracted from the medicinal and edible Dendrobium officinale , the DOP-based carrier we designed is promising to be developed for enhanced photodynamic immunotherapy in clinic.
Background: The mechanism ofDendrobium officinalepolysaccharide-based nanocarriers in enhancing photodynamic immunotherapy in colorectal cancer (CRC) remains poorly understood.Methods: The effects of TPA-3BCP-loaded cholesteryl hemisuccinate–Dendrobium officinalepolysaccharide nanoparticles (DOP@3BCP NPs) and their potential molecular mechanism of action in a tumor-bearing mouse model of CRC were investigated using non-targeted metabolomics and transcriptomics. Meanwhile, a histopathological analysis (H&E staining, Ki67 staining, and TUNEL assay) and a qRT-PCR analysis revealed the antitumor effects of DOP@3BCP NPs with and without light activation.Results: Through metabolomics and transcriptomics analysis, we found an alteration in the metabolome and functional pathways in the examined tumor tissues. The metabolic analysis showed 69 and 60 differentially expressed metabolites (DEMs) in positive- and negative-ion modes, respectively, in the treated samples compared to the Control samples. The transcriptomics analysis showed that 1352 genes were differentially expressed among the three groups. The differentially regulated functional pathways were primally related to the antitumor immune response. The results of the pathological histology assay and qRT-PCR analysis verified the findings of the integrated metabolomics and transcriptomics analysis.Conclusions: Overall, our findings elucidate the potential antitumor mechanisms of theD. officinalepolysaccharide-based nanocarrier in enhancing photodynamic immunotherapy in CRC.
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