Nanomedicine for colorectal cancer therapy by remodeling the immune microenvironment

Colorectal cancer (CRC), a malignant tumor with high incidence and mortality rates, poses a significant threat to human health. Although immunotherapeutic strategies such as immune checkpoint inhibitors (ICIs) have shown promising progress, limited efficacy, autoimmune side effects, systemic toxicity, and drug resistance remain major challenges in CRC immunotherapy. The complex tumor immune microenvironment (TIME), shaped by long-term interactions between cancer cells and microenvironmental components, is a key factor contributing to the poor response of most CRC patients to immunotherapy. With a deeper understanding of the TIME, nanomedicines have emerged as an effective strategy to remodel the TIME and achieve synergistic anti-tumor effects through targeted delivery of immunotherapeutic agents or multimodal combination therapeutic drugs. Based on the characteristic features of the TIME in CRC, this review summarizes recent advances in emerging preclinical nanomedicine-based strategies for TIME regulation in CRC treatment. Furthermore, it provides perspectives on the challenges and opportunities of nanomedicines in modulating the TIME of CRC. Acquisition of knowledge of nanomedicine-based reprogramming of the TIME holds great potential to advance precision immunotherapy for CRC toward clinical translation.