Nanoparticle delivery of Chinese medicine monomers for remodeling the colorectal cancer immune microenvironment

The colorectal cancer (CRC) microenvironment is typically “cold,” characterized by sparse immune infiltration and complex immunosuppressive networks, which limits the efficacy of immune checkpoint blockade (ICB). Traditional Chinese medicine (TCM) active monomers (such as curcumin, resveratrol, paclitaxel, and ginsenosides) possess inherent advantages in multi-target and multi-pathway anti-tumor immune regulation, but their clinical translation is hindered by low solubility, short half-life, and insufficient targeting. The purpose of this review is to summarize the recent progress of utilizing nanoparticle formulations of TCM monomers to reshape the CRC immune microenvironment and overcome these delivery obstacles. Relevant literature on the nano-delivery of TCM monomers for CRC immunotherapy was systematically searched across major databases including PubMed, Web of Science, and CNKI, using keywords such as “colorectal cancer,” “tumor microenvironment,” “nanoparticle,” “traditional Chinese medicine,” and “active monomers”. Relevant articles were screened, analyzed, and reviewed. Nanoparticle-delivered TCM monomers play a promising role in reshaping the CRC microenvironment through mechanisms classified into three dimensions: (1) “igniting” anti-tumor immunity by inducing immunogenic cell death (ICD), pyroptosis, and cGAS-STING activation; (2) improving the innate immune “soil” by reprogramming tumor-associated macrophages (TAMs) and promoting dendritic cell (DC) maturation; and (3) “normalizing” physical and chemical barriers by alleviating hypoxia, regulating abnormal metabolism, and remodeling the tumor stroma. Nano-delivery technologies serve as a promising strategy to unlock the therapeutic potential of TCM monomers in CRC treatment. Despite significant preclinical progress, translational challenges remain, including long-term nanomaterial biosafety, scalable manufacturing barriers, and the limitations of traditional animal models in capturing human CRC immune heterogeneity. Future integration of materials science, pharmaceutics, and immunology may facilitate the development of smart nano-formulations, overcoming these bottlenecks and opening new avenues for combination immunotherapy in advanced CRC.