Cancer-Immunity Cycle-Based Smart Nucleic Acid Nanodrugs for Potentiated Immunotherapy

The cancer-immunity cycle represents a self-amplifying cascade that is essential for generating durable antitumor immune responses. However, disruption of any individual step can render the entire cycle ineffective, thereby limiting the efficiency of cancer immunotherapy. Nucleic acid-based nanodrugs (NANDs) elicit unique interactions with both cancerous and immune cells, showing great potential in reactivating or amplifying the cancer-immunity cycle. This review first provides a brief introduction to the cancer-immunity cycle and NANDs and then outlines the major types of nonviral nanocarriers that have been developed to construct NANDs so far. Rational design strategies for smart NANDs are summarized. The recent advances in the precise modulation of each critical step within the cancer-immunity cycle by NANDs for enhanced cancer immunotherapy are highlighted. The current challenges faced by these NANDs are also briefly discussed.