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Life sciences · Journal article
Communications Biology · September 19, 2026
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Colorectal cancer ranks as the third most common cancer and the second leading cause of cancer-related mortality worldwide. Kaempferol is a natural flavonoid with reported anti-colorectal cancer activity, but its clinical application is limited by poor solubility and low bioavailability. Here we show that hyaluronic acid-modified, pH-sensitive liposomes effectively deliver kaempferol (KA/HLP). KA/HLP exhibit favorable stability and pH-responsive release and significantly enhance the antitumor efficacy of kaempferol in vitro and in vivo. Mechanistically, KA/HLP activate the cGAS/STING pathway to amplify innate immunity while dismantling PD-L1-mediated adaptive resistance. These effects are accompanied by enhanced antitumor immunity, characterized by increased dendritic cell maturation, cytotoxic T cell activation, a pro-inflammatory phenotype in tumor-associated macrophages, and reduced immunosuppressive cell infiltration. Furthermore, KA/HLP improve the therapeutic efficacy of PD-L1 blockade. Collectively, these findings identify KA/HLP as a promising nanoplatform for colorectal cancer immunotherapy by integrating efficient drug delivery with immune modulation. A hyaluronic acid-modified pH-sensitive liposome enables targeted delivery of kaempferol for colorectal cancer therapy. The formulation improves kaempferol stability, cellular uptake, and antitumor activity while promoting antitumor immune responses.