Tao Shengchang, Wang Huan, Ji Qiufeng, Yang Yushan, Wei Gang, Li Ruiming, Zhou Benjie
Department of Pharmacy, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen 518107, China.
Shenzhen Key Laboratory of Chinese Medicine Active Substance Screening and Translational Research, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen 518107, China.
Pharmaceutics. 2025 Jan 13;17(1):97. doi: 10.3390/pharmaceutics17010097.
: The mechanism of polysaccharide-based nanocarriers in enhancing photodynamic immunotherapy in colorectal cancer (CRC) remains poorly understood. : The effects of TPA-3BCP-loaded cholesteryl hemisuccinate- polysaccharide 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. : 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. : Overall, our findings elucidate the potential antitumor mechanisms of the polysaccharide-based nanocarrier in enhancing photodynamic immunotherapy in CRC.
基于多糖的纳米载体增强结直肠癌（CRC）光动力免疫治疗的机制仍知之甚少。使用非靶向代谢组学和转录组学研究了负载三苯基胺-3-溴代氯苯卟啉（TPA-3BCP）的胆固醇半琥珀酸酯-多糖纳米颗粒（DOP@3BCP NPs）在CRC荷瘤小鼠模型中的作用及其潜在的分子作用机制。同时，组织病理学分析（苏木精-伊红染色、Ki67染色和TUNEL检测）和qRT-PCR分析揭示了有无光激活情况下DOP@3BCP NPs的抗肿瘤作用。通过代谢组学和转录组学分析，我们发现所检测肿瘤组织的代谢组和功能途径发生了改变。代谢分析表明，与对照样品相比，处理样品在正离子和负离子模式下分别有69种和60种差异表达代谢物（DEM）。转录组学分析表明，三组之间有1352个基因差异表达。差异调节的功能途径主要与抗肿瘤免疫反应相关。病理组织学检测和qRT-PCR分析结果证实了综合代谢组学和转录组学分析的结果。总体而言，我们的研究结果阐明了基于多糖的纳米载体在增强CRC光动力免疫治疗中的潜在抗肿瘤机制。
