Nanodynamic therapy for cancer: mechanistic innovations, targeting strategies and multimodal treatments

Nanodynamic therapy (NDT), as an emerging cancer treatment strategy, achieves specific killing of tumor cells by using nanomaterials to generate reactive oxygen species (ROS) under the activation of external energies (e.g. light, acoustic, thermal, and electrical, etc.). This article systematically reviews the classification of NDT and its mechanism of action, including photodynamic therapy (PDT), sonodynamic therapy (SDT), thermodynamic therapy (TDT), etc. and explores in detail the multiple pathways of tumor cell death (e.g. apoptosis, iron-death, copper-death, and cell-cycle blockade) induced by NDT. In addition, the article focuses on analyzing the targeting strategies (e.g. targeting peptides, nucleic acids, folate receptors, and mitochondrial targeting) and drug delivery systems (e.g. exosomes, liposomes, and nano-metal-organic frameworks) of NDT to enhance the precision and efficiency of the treatment. By combining chemotherapy, immunotherapy and bacterial therapy, NDT further overcomes tumor microenvironmental limitations and enhances therapeutic efficacy. Clinical studies have demonstrated the potential of NDT in the treatment of brainstem glioma and prostate cancer. Future studies should focus on optimizing sensitizer design, improving the tumor hypoxic microenvironment, and developing multifunctional nanoplatforms to promote the clinical translation of NDT.