Nanomedicine for targeting cancer-associated fibroblasts in cancer therapy

Cancer-associated fibroblasts (CAFs) play a crucial role in the tumor microenvironment, where they facilitate tumor progression, angiogenesis, immune evasion, and treatment resistance, highlighting the urgent need for CAF-targeted strategies for high-performance tumor therapy. Recent nanomedicine approaches have shown promise in CAFs targeting in order to achieve precise targeting, spatiotemporal control of drug release, and enhanced drug penetration into dense fibrotic stroma. Accordingly, this review summarizes emerging nanotechnologies that address challenges through the development of functional nanomaterials for CAFs targeting, including polymers, metal and non-metal inorganic nanoparticles (NPs), cell membrane-based NPs, and protein-based NPs. Specifically, various therapeutic approaches such as direct CAFs depletion, signaling pathway modulation in CAFs, and CAFs reprogramming by using these nanomedicines are discussed. Furthermore, potential avenues for future studies, including the development of versatile nanosystems and the exploration of personalized treatment regimens, and challenges of advanced functional nanomaterials are involved as well. We hope that this review will offer new insights into cancer therapy and advance the development of clinically applicable CAF-targeted nanomedicines.